Updated on 2024/06/15

写真a

 
YURA, Kei
 
Affiliation
Faculty of Science and Engineering, School of Advanced Science and Engineering
Job title
Professor(without tenure)
Degree
(BLANK) ( Waseda University )
(BLANK) ( Nagoya University )

Research Experience

  • 2019.05
    -
    Now

    Ochanomizu University   Headquarters for Research and Innovation, Research Advancement Division, Education and Research Department Center for Interdisciplinary AI and Data Science   Vice Director

  • 2017.04
    -
    Now

    Waseda University   School of Advanced Science and Engineering   Professor

  • 2016.04
    -
    2019.03

    Ochanomizu University   President

  •  
     
     

    Waseda University Faculty of Science and Engineering

  •  
     
     

    Ochanomizu University Graduate School of Humanities and Sciences   Professor

Education Background

  •  
    -
    1993

    Nagoya University  

  •  
    -
    1993

    Nagoya University   Graduate School, Division of Natural Science  

  •  
    -
    1988

    Waseda University   School of Science and Engineering  

  •  
    -
    1988

    Waseda University   Faculty of Science and Engineering  

Committee Memberships

  • 2019.10
    -
    2020.10

    日本生物物理学会  2020年会実行委員会副委員長

  • 2011.01
    -
    2012.12

    The Biophysical Society of Japan  vice president

  • 2007
    -
     

    日本生物物理学会  運営委員

Professional Memberships

  •  
     
     

    米国生物物理学会

  •  
     
     

    日本蛋白質科学会

  •  
     
     

    日本分子生物学会

  •  
     
     

    日本生物物理学会

Research Areas

  • Biophysics / System genome science / Genome biology / Life, health and medical informatics

Research Interests

  • Biophysics

  • Computational biology

 

Papers

  • Complete mitochondrial genome sequences of two ground crickets, Dianemobius fascipes nigrofasciatus and Polionemobius taprobanensis (Orthoptera: Grylloidea: trigonidiidae)

    Kohyoh Murata, Kosuke Kataoka, Ryuto Sanno, Kazuhiro Satomura, Atsushi Ogura, Toru Asahi, Kei Yura, Takeshi Suzuki

    Mitochondrial DNA Part B   8 ( 12 ) 1311 - 1315  2023.12

    DOI

    Scopus

  • ThermusQ: Toward the cell simulation platform for Thermus thermophilus.

    Atsushi Hijikata, Tairo Oshima, Kei Yura, Yoshitaka Bessho

    The Journal of general and applied microbiology    2023.07  [Refereed]  [Domestic journal]

     View Summary

    ThermusQ is a website that aims to gather all the molecular information on Thermus thermophilus and to provide a platform to easily access the whole view of the bacterium. ThermusQ comprises the genome sequences of 22 strains from T. thermophilus and T. oshimai strains, plus the sequences of known Thermus phages. ThermusQ also contains information and map diagrams of pathways unique to Thermus strains. The website provides tools to retrieve sequence data in different ways. By gathering the whole data of T. thermophilus strains, the strainspecific characteristics was found. This bird's-eye view of the whole data will lead the research community to identify missing important data and the integration will provide a platform to conduct future biochemical simulations of the bacterium.

    DOI PubMed

    Scopus

  • Isolation and genomic analysis of a type IV pili-independent Thermus thermophilus phage, φMN1 from a Japanese hot spring.

    Masatada Tamakoshi, Atsushi Hijikata, Kei Yura, Kenshiro Oshima, Hidehiro Toh, Kaoru Mitsuoka, Tairo Oshima, Yoshitaka Bessho

    The Journal of general and applied microbiology    2023.07  [Refereed]  [Domestic journal]

     View Summary

    A Thermus thermophilus lytic phage was isolated from a Japanese hot spring by using a type IV pili-deficient strain as an indicator host, and designated as φMN1. Electron microscopic (EM) examination revealed that φMN1 had an icosahedral head and a contractile tail, suggesting that φMN1 belonged to Myoviridae. An EM analysis focused on φMN1 adsorption to the Thermus host cell showed that the receptor molecules for the phage were uniformly distributed on the outer surface of the cells. The circular double-stranded DNA of φMN1 was 76,659 base pairs in length, and the guanine and cytosine content was 61.8%. It was predicted to contain 99 open reading frames, and its putative distal tail fiber protein, which is essential for non-piliated host cell surface receptor recognition, was dissimilar in terms of sequence and length with its counterpart in the type IV pili-dependent φYS40. A phage proteomic tree revealed that φMN1 and φYS40 are in the same cluster, but many genes had low sequence similarities and some seemed to be derived from both mesophilic and thermophilic organisms. The gene organization suggested that φMN1 evolved from a non-Thermus phage through large-scale recombination events of the genes determining the host specificity, followed by gradual evolution by recombination of both the thermophilic and mesophilic DNAs assimilated by the host Thermus cells. This newly isolated phage will provide evolutionary insights into thermophilic phages.

    DOI PubMed

    Scopus

  • Whole genome analyses for c-type cytochromes associated with respiratory chains in the extreme thermophile, Thermus thermophilus.

    Koyu Hon-Nami, Atsushi Hijikata, Kei Yura, Yoshitaka Bessho

    The Journal of general and applied microbiology    2023.06  [Refereed]  [Domestic journal]

     View Summary

    In thermophilic microorganisms, c-type cytochrome (cyt) proteins mainly function in the respiratory chain as electron carriers. Genome analyses at the beginning of this century revealed a variety of genes harboring the heme c motif. Here, we describe the results of surveying genes with the heme c motif, CxxCH, in a genome database comprising four strains of Thermus thermophilus, including strain HB8, and the confirmation of 19 c-type cytochromes among 27 selected genes. We analyzed the 19 genes, including the expression of four, by a bioinformatics approach to elucidate their individual attributes. One of the approaches included an analysis based on the secondary structure alignment pattern between the heme c motif and the 6th ligand. The predicted structures revealed many cyt c domains with fewer β-strands, such as mitochondrial cyt c, in addition to the β-strand unique to Thermus inserted in cyt c domains, as in T. thermophilus cyt c552 and caa3 cyt c oxidase subunit IIc. The surveyed thermophiles harbor potential proteins with a variety of cyt c folds. The gene analyses led to the development of an index for the classification of cyt c domains. Based on these results, we propose names for T. thermophilus genes harboring the cyt c fold.

    DOI PubMed

    Scopus

    1
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  • PGLN: A newly identified amino phosphoglycolipid species in Thermus thermophilus HB8.

    Naoki Nemoto, Masahiko Kawaguchi, Kei Yura, Haruo Shimada, Yoshitaka Bessho

    Biochemistry and biophysics reports   32   101377 - 101377  2022.12  [Refereed]  [International journal]

     View Summary

    Thermus thermophilus has several minor lipid molecules with structures that have not been described yet. In this study, we identified a new lipid molecule in T. thermophilus HB8 with an amino group at the polar head, by detecting lipid spots with HPTLC and mass spectrometry. The structure of the lipid resembles an amino sugar phospholipid, except for the glucosamine that lacks an acetyl group. We named this amino phosphoglycolipid PGLN, and proposed its synthetic pathway from a precursor, phosphatidyl-glyceric alkylamine. The primary amine structure of PGLN may contribute to high temperature adaptation through electrostatic interactions between the head groups.

    DOI PubMed

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    3
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  • Validation of the application of gel beads-based single-cell genome sequencing platform to soil and seawater

    Yohei Nishikawa, Masato Kogawa, Masahito Hosokawa, Ryota Wagatsuma, Katsuhiko Mineta, Kai Takahashi, Keigo Ide, Kei Yura, Hayedeh Behzad, Takashi Gojobori, Haruko Takeyama

    ISME Communications   2 ( 1 )  2022.09  [Refereed]

     View Summary

    Abstract

    Single-cell genomics is applied to environmental samples as a method to solve the problems of current metagenomics. However, in the fluorescence-activated cell sorting-based cell isolation and subsequent whole genome amplification, the sorting efficiency and the sequence quality are greatly affected by the type of target environment, limiting its adaptability. Here, we developed an improved single-cell genomics platform, named SAG-gel, which utilizes gel beads for single-cell isolation, lysis, and whole genome amplification. To validate the versatility of SAG-gel, single-cell genome sequencing was performed with model bacteria and microbial samples collected from eight environmental sites, including soil and seawater. Gel beads enabled multiple lysis treatments. The genome coverage with model bacteria was improved by 9.1–25%. A total of 734 single amplified genomes were collected from the diverse environmental samples, and almost full-length 16S rRNA genes were recovered from 57.8% of them. We also revealed two marine Rhodobacter strains harboring nearly identical 16S rRNA genes but having different genome contents. In addition, searching for viral sequences elucidated the virus-host linkage over the sampling sites, revealing the geographic distribution and diverse host range of viruses.

    DOI

  • ADAMTS2 regulates radial neuronal migration by activating TGF-β signaling at the subplate layer of the developing neocortex

    Noe Kaneko, Kumiko Hirai, Minori Oshima, Kei Yura, Mitsuharu Hattori, Nobuaki Maeda, Chiaki Ohtaka-Maruyama

       2022.08  [Refereed]

     View Summary

    ABSTRACT

    During the development of the mammalian brain, neocortical structures are formed by the sequential radial migration of newborn excitatory neurons. The early migrating neurons exhibit a multipolar shape, but they undergo a multipolar-to-bipolar transition at the subplate (SP) layer, where extracellular matrix (ECM) components are abundantly expressed. In this study, we revealed that the TGF-β signaling-related ECM proteins, such as latent TGF-β-binding protein 1 (LTBP1) and fibrillin 2, and TGF-β receptor II (TGF-βRII) and its downstream effector, p-smad2/3, are selectively expressed at the SP layer, suggesting that TGF-β is sequestered in a latent form by forming complexes with these ECM components and then its signaling is activated by ECM remodeling. We found that the migrating multipolar neurons transiently express a disintegrin and metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. Knockdown and knockout of Adamts2 suppressed the multipolar-to-bipolar transition of migrating neurons, and therefore, disturbed radial migration. Similar phenotypes were observed by the perturbation of TGF-β signaling in the migrating neurons. Time-lapse luminescence imaging of TGF-β signaling indicated that ADAMTS2 activates this signaling pathway in the migrating neurons during the multipolar-to-bipolar transition at the SP layer. These results suggest that the ADAMTS2 secreted by the migrating multipolar neurons activates TGF-β signaling by ECM remodeling of the SP layer, leading to the multipolar-to-bipolar transition. We propose that the SP layer plays an essential role in the radial neuronal migration as a signaling center of the developing neocortex.

    SIGNIFICANCE

    The neocortex is formed by the sequential radial migration of newborn neurons, which undergo a multipolar-to-bipolar transition at the subplate (SP) layer. The extracellular matrix (ECM) is abundantly expressed in the SP layer. However, the roles of the ECM in the SP layer have been unclear. We found that migrating neurons transiently express a disintegrin and a metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. We show that ADAMTS2 secreted by multipolar migrating neurons activates TGF-β signaling through remodeling of the ECM in the SP layer, leading to the multipolar-to-bipolar transition. Thus, the SP layer plays an essential role in radial migration as a signaling center of the developing neocortex

    DOI

  • 難病医療における遺伝カウンセリングに関する動画教材の作成

    佐々木 元子, 川目 裕, 松尾 真理, 小杉 眞司, 櫻井 晃洋, 由良 敬, 高島 響子, 李 怡然, 松川 愛未, 大住 理沙, 神原 容子, 三宅 秀彦

    日本遺伝カウンセリング学会誌   43 ( 2 ) 144 - 144  2022.06

  • Targeted single-cell genomics reveals novel host adaptation strategies of the symbiotic bacteria Endozoicomonas in Acropora tenuis coral

    Keigo Ide, Yohei Nishikawa, Toru Maruyama, Yuko Tsukada, Masato Kogawa, Hiroki Takeda, Haruka Ito, Ryota Wagatsuma, Rimi Miyaoka, Yoshikatsu Nakano, Koji Kinjo, Michihiro Ito, Masahito Hosokawa, Kei Yura, Shoichiro Suda, Haruko Takeyama

    bioRxiv    2022.04

     View Summary

    Abstract

    Endozoicomonas bacteria symbiose with various marine organisms and are known to be beneficial for coral health. However, genome analysis of coral-associated Endozoicomonas has been limited owing to the difficulty in cultivation and metagenomic approach by contamination of host-derived sequences. In this study, we applied a novel single-cell genomics technique using droplet microfluidics to obtain single-cell amplified genome (SAGs) for coral-associated Endozoicomonas spp. genome. We obtained seven novel Endozoicomonas genomes from Acropora tenuis coral. These genomes revealed that Endozoicomonas bacteria played host-associated functions in host corals and had undergone independent host-adaptive evolution in different clades. These adaptive evolutions were mediated by host-derived eukaryotic-like genes, some of which were speculated to influence host immune mechanisms. These genes are speculated to enhance coral tolerance to environmental stresses. This study suggests the possibility of host adaptation of Endozoicomonas spp. in symbiosis with corals and their contribution to coral bleaching tolerance.

    DOI

  • Co-expression network analysis of environmental canalization in the ascidian Ciona

    Atsuko Sato, Gina M Oba, Nathanael Aubert-Kato, Kei Yura, John Bishop

    BMC Ecology and Evolution   22   53 - 53  2022.04  [Refereed]

  • Single-cell metabolite detection and genomics reveals uncultivated talented producer

    Masato Kogawa, Rimi Miyaoka, Franziska Hemmerling, Masahiro Ando, Kei Yura, Keigo Ide, Yohei Nishikawa, Masahito Hosokawa, Yuji Ise, Jackson K B Cahn, Kentaro Takada, Shigeki Matsunaga, Tetsushi Mori, Jörn Piel, Haruko Takeyama

    PNAS Nexus   1 ( 1 )  2022.03  [Refereed]

     View Summary

    Abstract

    The production of bioactive metabolites is increasingly recognized as an important function of host-associated bacteria. An example is defensive symbiosis that might account for much of the chemical richness of marine invertebrates including sponges (Porifera), 1 of the oldest metazoans. However, most bacterial members of sponge microbiomes have not been cultivated or sequenced, and therefore, remain unrecognized. Unequivocally linking metabolic functions to a cellular source in sponge microbiomes is, therefore, a challenge. Here, we report an analysis pipeline of microfluidic encapsulation, Raman microscopy, and integrated digital genomics (MERMAID) for an efficient identification of uncultivated producers. We applied this method to the chemically rich bacteriosponge (sponge that hosts a rich bacterial community) Theonella swinhoei, previously shown to contain ‘Entotheonella’ symbionts that produce most of the bioactive substances isolated from the sponge. As an exception, the antifungal aurantosides had remained unassigned to a source. Raman-guided single-bacterial analysis and sequencing revealed a cryptic, distinct multiproducer, ‘Candidatus Poriflexus aureus’ from a new Chloroflexi lineage as the aurantoside producer. Its exceptionally large genome contains numerous biosynthetic loci and suggested an even higher chemical richness of this sponge than previously appreciated. This study highlights the importance of complementary technologies to uncover microbiome functions, reveals remarkable parallels between distantly related symbionts of the same host, and adds functional support for diverse chemically prolific lineages being present in microbial dark matter.

    DOI

    Scopus

    13
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  • CFI 25 subunit of cleavage factor I is important for maintaining the diversity of 3′ UTR lengths in Arabidopsis thaliana (L.) Heynh

    Xiaojuan Zhang, Mika Nomoto, Marta Garcia-León, Naoki Takahashi, Mariko Kato, Kei Yura, Masaaki Umeda, Vicente Rubio, Yasuomi Tada, Tsuyoshi Furumoto, Takashi Aoyama, Tomohiko Tsuge

    Plant and Cell Physiology   63 ( 3 ) 369 - 383  2022.01  [Refereed]

     View Summary

    Abstract

    Cleavage and polyadenylation at the 3ʹ end of the pre-mRNA is essential for mRNA function, by regulating its translatability, stability and translocation to the cytoplasm. Cleavage factor I (CFI) is a multi-subunit component of the pre-mRNA 3ʹ end processing machinery in eukaryotes. Here, we report that plant CFI 25 subunit of CFI plays an important role in maintaining the diversity of the 3ʹ ends of mRNA. The genome of Arabidopsis thaliana (L.) Heynh. contained four genes encoding three putative CFI subunits (AtCFI 25, AtCFI 59 and AtCFI 68), orthologous to the mammalian CFI subunits. There were two CFI 25 paralogs (AtCFI 25a and AtCFI 25b) that shared homology with human CFI 25. Two null alleles of AtCFI 25a displayed smaller rosette leaves, longer stigmatic papilla, smaller anther, earlier flowering and lower fertility compared to wild-type plants. Null alleles of AtCFI 25b, as well as, plants ectopically expressing full-length cDNA of AtCFI 25a, displayed no obvious morphological defects. AtCFI 25a was shown to interact with AtCFI 25b, AtCFI 68 and itself, suggesting various forms of CFI in plants. Furthermore, we show that AtCFI 25a function was essential for maintaining proper diversity of the 3ʹ end lengths of transcripts coding for CFI subunits, suggesting a self-regulation of the CFI machinery in plants. AtCFI 25a was also important to maintain 3ʹ ends for other genes to different extent. Collectively, AtCFI 25a, but not AtCFI 25b, seemed to play important roles during Arabidopsis development by maintaining proper diversity of the 3ʹ UTR lengths.

    DOI

    Scopus

    2
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  • Dissecting Cricket Genomes for Advancement of Entomology and Entomophagy

    Kosuke Kataoka, Yuki Togawa, Ryuto Sanno, Toru Asahi, Kei Yura

    Biophysical Reviews   14   75 - 97  2022.01  [Refereed]

  • Puromycin-based purification of cells with high expression of the cytochrome P450 CYP3A4 gene from a patient with drug-induced liver infury (DILI)

    Shoko Miyata, Noriaki Saku, Saeko Akiyama, Palaksha Kanive, Javaregowda, Kenta Ite, Nagisa Takashima, Masashi Toyoda, Kei Yura, Tohru Kimura, Hiroshi Nishina, Atsuko Nakazawa, Mureo Kasahara, Hidenori Nonaka, Tohru Kiyono, Akihiro Umezawa

    Stem Cell Research & Therapy   13 ( 1 ) 6 - 6  2022.01  [Refereed]  [International journal]

     View Summary

    BACKGROUND: Many drugs have the potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in hepatocytes. Hepatocytes can be accurately evaluated for drug-mediated CYP3A4 induction; this is the gold standard for in vitro hepatic toxicology testing. However, the variation from lot to lot is an issue that needs to be addressed. Only a limited number of immortalized hepatocyte cell lines have been reported. In this study, immortalized cells expressing CYP3A4 were generated from a patient with drug-induced liver injury (DILI). METHODS: To generate DILI-derived cells with high expression of CYP3A4, a three-step approach was employed: (1) Differentiation of DILI-induced pluripotent stem cells (DILI-iPSCs); (2) Immortalization of the differentiated cells; (3) Selection of the cells by puromycin. It was hypothesized that cells with high cytochrome P450 gene expression would be able to survive exposure to cytotoxic antibiotics because of their increased drug-metabolizing activity. Puromycin, a cytotoxic antibiotic, was used in this study because of its rapid cytocidal effect at low concentrations. RESULTS: The hepatocyte-like cells differentiated from DILI-iPSCs were purified by exposure to puromycin. The puromycin-selected cells (HepaSM or SI cells) constitutively expressed the CYP3A4 gene at extremely high levels and exhibited hepatocytic features over time. However, unlike primary hepatocytes, the established cells did not produce bile or accumulate glycogen. CONCLUSIONS: iPSC-derived hepatocyte-like cells with intrinsic drug-metabolizing enzymes can be purified from non-hepatocytes and undifferentiated iPSCs using the cytocidal antibiotic puromycin. The puromycin-selected hepatocyte-like cells exhibited characteristics of hepatocytes after immortalization and may serve as another useful source for in vitro hepatotoxicity testing of low molecular weight drugs.

    DOI PubMed

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    10
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  • Protein Data Bank Japan: Celebrating our 20th anniversary during a global pandemic as the Asian hub of three dimensional macromolecular structural data.

    Gert-Jan Bekker, Masashi Yokochi, Hirofumi Suzuki, Yasuyo Ikegawa, Takeshi Iwata, Takahiro Kudou, Kei Yura, Toshimichi Fujiwara, Takeshi Kawabata, Genji Kurisu

    Protein science : a publication of the Protein Society   31 ( 1 ) 173 - 186  2022.01  [Refereed]  [International journal]

     View Summary

    Protein Data Bank Japan (PDBj), a founding member of the worldwide Protein Data Bank (wwPDB) has accepted, processed and distributed experimentally determined biological macromolecular structures for 20 years. During that time, we have continuously made major improvements to our query search interface of PDBj Mine 2, the BMRBj web interface, and EM Navigator for PDB/BMRB/EMDB entries. PDBj also serves PDB-related secondary database data, original web-based modeling services such as Homology modeling of complex structure (HOMCOS), visualization services and utility tools, which we have continuously enhanced and expanded throughout the years. In addition, we have recently developed several unique archives, BSM-Arc for computational structure models, and XRDa for raw X-ray diffraction images, both of which promote open science in the structural biology community. During the COVID-19 pandemic, PDBj has also started to provide feature pages for COVID-19 related entries across all available archives at PDBj from raw experimental data and PDB structural data to computationally predicted models, while also providing COVID-19 outreach content for high school students and teachers.

    DOI PubMed

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    26
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  • Multi-omics analysis reveals cross-organism interactions in coral holobiont

    Toru Maruyama, Michihiro Ito, Satoshi Wakaoji, Yusuke Okubo, Keigo Ide, Yohei Nishikawa, Hiroyuki Fujimura, Shoichiro Suda, Yoshikatsu Nakano, Noriyuki Satoh, Chuya Shinzato, Kei Yura, Haruko Takeyama

    bioRxiv    2021.10

     View Summary

    Abstract

    Corals create an ecosystem, called a holobiont, with intracellular algae (zooxanthellae) and resident bacteria. Zooxanthellae and some bacteria play major roles in the physiological properties of the coral host. However, because of the difficulties in experimental verification of cross-organism interactions, the mechanisms underpinning these interactions are largely unknown. To address this, we here generated and then analyzed multi-omics datasets for corals, zooxanthellae, and bacteria collected at Okinawa, Japan, from November 2014 to September 2016. Using cross-organism co-expression analysis, we successfully characterized the host–alga relationship in the coral holobiont. Specifically, we observed that the coral host dominates the zooxanthellae. The multi-omics analysis also suggested that infection with coral-associated bacteria Endozoicomonas likely involves coral-like ephrin ligands, triggering an immune response of the coral host. This study highlights the potential of the multi-omics approach to elucidate coral–microbe interactions.

    DOI

  • Comparative Analysis of Mitochondrial Genomes in Gryllidea (Insecta: Orthoptera): Implications for Adaptive Evolution in Ant-loving Crickets.

    Ryuto Sanno, Kosuke Kataoka, Shota Hayakawa, Keigo Ide, Chuong N Nguyen, Thao P Nguyen, Binh T N Le, Oanh T P Kim, Katsuhiko Mineta, Haruko Takeyama, Makio Takeda, Toshiyuki Sato, Takeshi Suzuki, Kei Yura, Toru Asahi

    Genome biology and evolution   13 ( 10 )  2021.09  [International journal]

     View Summary

    Species of infraorder Gryllidea, or crickets, are useful invertebrate models for studying developmental biology and neuroscience. They have also attracted attention as alternative protein sources for human food and animal feed. Mitochondrial genomic information on related invertebrates, such as katydids, and locusts, has recently become available in attempt to clarify the controversial classification schemes, although robust phylogenetic relationships with emphasis on crickets remain elusive. Here, we report newly sequenced complete mitochondrial genomes of crickets to study their phylogeny, genomic rearrangements, and adaptive evolution. First, we conducted de novo assembly of mitochondrial genomes from eight cricket species and annotated protein-coding genes (PCGs) and transfer and ribosomal RNAs using automatic annotations and manual curation. Next, by combining newly described PCGs with public data of the complete Gryllidea genomes and gene annotations, we performed phylogenetic analysis and found gene order rearrangements in several branches. We further analyzed genetic signatures of selection in ant-loving crickets (Myrmecophilidae), which are small wingless crickets that inhabit ant nests. Three distinct approaches revealed two positively selected sites in the cox1 gene in these crickets. Protein 3D structural analyses suggested that these selected sites could influence the interaction of respiratory complex proteins, conferring benefits to ant-loving crickets with a unique ecological niche and morphology. These findings enhance our understanding of the genetic basis of cricket evolution without relying on estimates based on a limited number of molecular markers.

    DOI PubMed

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  • Survey on genomic counseling education

    佐々木元子, 佐々木元子, 川目裕, 小杉眞司, 櫻井晃洋, 松尾真理, 由良敬, 由良敬, 由良敬, 高島響子, 李怡然, 松川愛未, 神原容子, 三宅秀彦, 三宅秀彦

    日本遺伝カウンセリング学会誌   42 ( 2 ) 118 - 118  2021.06

    J-GLOBAL

  • Edible wild field cricket (Brachytrupes portentosus) trading in Bangladesh.

    Md. Mehedi Hasan, Md. Mostafizur Rahman, Kosuke Kataoka, Kei Yura, Md. Omar Faruque, Faysal Rabby Shadhen, Md Fuad Mondal

    Journal of Insects as Food and Feed   7 ( 8 ) 1255 - 1126  2021.06  [Refereed]

  • Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen degrading enzyme cathepsin K activity

    Kimie Date, Hiromi Sakagami, Kei Yura

    Scientific Reports   11   12023  2021.06  [Refereed]

  • Multiple Mutations in RNA Polymerase β-Subunit Gene (rpoB) in Streptomyces incarnatus NRRL8089 Enhance Production of Antiviral Antibiotic Sinefungin: Modeling rif Cluster Region by Density Functional Theory

    Saori Ogawa, Hitomi Shimidzu, Koji Fukuda, Naoki Tsunekawa, Toshiyuki Hirano, Fumitoshi Sato, Kei Yura, Tomohisa Hasunuma, Kozo Ochi, Michio Yamamoto, Wataru, Sakamoto, Kentaro Hashimoto, Hiroyuki Ogata, Tadayoshi Kanao, Michiko Nemoto, Kenji Inagaki, Takashi Tamura

    Bioscience, Biotechnology and Biochemistry   85 ( 5 ) 1275 - 1282  2021.05  [Refereed]  [International journal]

     View Summary

    Streptomyces incarnatus NRRL8089 produces the antiviral, antifungal, antiprotozoal nucleoside antibiotic sinefungin. To enhance sinefungin production, multiple mutations were introduced to the rpoB gene encoding RNA polymerase (RNAP) β-subunit at the target residues, D447, S453, H457, and R460. Sparse regression analysis using elastic-net lasso-ridge penalties on previously reported H457X mutations identified a numeric parameter set, which suggested that H457R/Y/F may cause production enhancement. H457R/R460C mutation successfully enhanced the sinefungin production by 3-fold, while other groups of mutations, such as D447G/R460C or D447G/H457Y, made moderate or even negative effects. To identify why the rif cluster residues have diverse effects on sinefungin production, an RNAP/DNA/mRNA complex model was constructed by homology modeling and molecular dynamics simulation. The 4 residues were located near the mRNA strand. Density functional theory-based calculation suggested that D447, H457, and R460 are in direct contact with ribonucleotide, and partially positive charges are induced by negatively charged chain of mRNA.

    DOI PubMed

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  • Complete Genome Sequences of Thermus thermophilus Strains HB5002 and HB5008, Isolated from Mine Hot Spring in Japan

    Kentaro Miyazaki, Toshiyuki Moriya, Natsuko Tokito, Tairo Oshima, Kei Yura, Yoshitaka Bessho

    Microbiology Resource Announcements   10   e00272-21  2021.04  [Refereed]

  • SAP130 and CSN1 interact and regulate male gametogenesis in Arabidopsis thaliana

    Shiori S. Aki, Kei Yura, Takashi Aoyama, Tomohiko Tsuge

    Journal of Plant Research   134 ( 2 ) 279 - 289  2021.03  [Refereed]  [Domestic journal]

     View Summary

    COP9 signalosome (CSN) is a nuclear complex composed of eight distinct subunits that governs vast developmental processes in Arabidopsis thaliana (L.) Heynh. The null alleles of csn mutants display pleiotropic phenotypes that result in seedling lethality. To date, several partially complemented transgenic plants, expressing the particular CSN subunit in its corresponding null mutant allele, were utilized to bypass seedling lethality and investigate CSN regulation at later stages of development. One such transgenic plant corresponding to CSN1 subunit, fus6/CSN1-3-4, accumulates wild-type level of CSN1 and displays normal plant architecture at vegetative stage. Here we show through histological analyses that fus6/CSN1-3-4 plants display impairment of pollen development at the bicellular stage. This defect is identical to that observed in RNAi plants of SAP130, encoding a subunit of the multiprotein splicing factor SF3b. We further dissected the previously reported interaction between CSN1 and SAP130, to reveal that approximately 100 amino-acid residues located at the N-terminal end of CSN1 (CSN1NN) were essential for this interaction. In silico structure modeling demonstrated that CSN1NN could swing out towards SAP130 to dock onto its Helical Insertion protruding from the structure. These results support our model that CSN1 embeds itself within CSN protein complex through its C-terminal half and reaches out to targets through its N-terminal portion of the protein. Taken together, this is the first report to document the identical loss-of-function phenotypes of CSN1 and SAP130 during male gametogenesis. Thus, we propose that SAP130 and CSN1 coordinately regulate development of male reproductive organs.

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  • Exploration of natural red-shifted rhodopsins using a machine learning-based Bayesian experimental design

    Keiichi Inoue, Masayuki Karasuyama, Ryoko Nakamura, Masae Konno, Daichi Yamada, Kentaro Mannen, Takashi Nagata, Yu Inatsu, Kei Yura, Oded Béjà, Hideki Kandori, Ichiro Takeuchi

    Communications Biology   4   362  2021.03  [Refereed]

  • Complete Genome Sequence of Thermus thermophilus Strain HB5018, Isolated from Mine Hot Spring in Japan

    Kentaro Miyazaki, Toshiyuki Moriya, Naoki Nemoto, Tairo Oshima, Kei Yura, Yoshitaka Bessho

    Microbiology Resource Announcements   10   e0039-21  2021.03  [Refereed]

  • A novel circular ssDNA virus of the phylum Cressdnaviricota discovered in metagenomic data from otter clams (Lutraria rhynchaena)

    Oanh T. P. Kim, Yuki Kagaya, Hoang S. Tran, Ryuhei Minei, Trang T. H. Tran, Ha T. T. Duong, Binh T. N. Le, Lua T. Dang, Kengo Kinoshita, Atsushi Ogura, Kei Yura

    Archives of Virology   165 ( 12 ) 2921 - 2926  2020.12  [Refereed]  [International journal]

     View Summary

    In this study, we present an analysis of metagenome sequences obtained from a filtrate of a siphon tissue homogenate of otter clams (Lutraria rhynchaena) with swollen-siphon disease. The viral signal was mined from the metagenomic data, and a novel circular ssDNA virus was identified. Genomic features and phylogenetic analysis showed that the virus belongs to the phylum Cressdnaviricota, which consists of viruses with circular, single-stranded DNA (ssDNA) genomes. Members of this phylum have been identified in various species and in environmental samples. The newly found virus is distantly related to the currently known members of the phylum Cressdnaviricota.

    DOI PubMed

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    2
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  • Genomic and Transcriptomic Analyses of Bioluminescence Genes in the Enope Squid Watasenia scintillans

    Masa-aki Yoshida, Junichi Imoto, Yuri Kawai, Satomi Funahashi, Ryuhei Minei, Yuki Akizuki, Atsushi Ogura, Kazuhiko Nakabayashi, Kei Yura, Kazuho Ikeo

    Marine Biotechnology   22 ( 6 ) 760 - 771  2020.12  [Refereed]  [Invited]  [International journal]

     View Summary

    <jats:title>Abstract</jats:title><jats:p><jats:italic>Watasenia scintillans</jats:italic>, a sparkling enope squid, has bioluminescence organs to illuminate its body with its own luciferase activity. To clarify the molecular mechanism underlying its scintillation, we analysed high-throughput sequencing data acquired previously and obtained draft genome sequences accomplished with comparative genomic data among the cephalopods. The genome mapped by transcriptome data showed that (1) RNA editing contributed to transcriptome variation of lineage specific genes, such as <jats:italic>W. scintillans</jats:italic> luciferase, and (2) two types of luciferase enzymes were characterized with reasonable 3D models docked to a luciferin molecule. We report two different types of luciferase in one organism and possibly related to variety of colour types in the <jats:italic>W. scintillans</jats:italic> fluorescent organs.</jats:p>

    DOI PubMed

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    3
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  • High-precision multiclass cell classification by supervised machine learning on lectin microarray data

    Mayu Shibata, Kohji Okamura, Kei Yura, Akihiro Umezawa

    Regenerative Therapy   15   195 - 201  2020.12  [Refereed]

    DOI

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    2
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  • Past, Present and Future of Ewha-JWU-Ochanomizu Joint Symposium

    Kei Yura

    Natural Science Report, Ochanomizu University    2020.09  [Refereed]  [Invited]  [Domestic journal]

  • Knowledge and attitude of hereditary breast cancer among Japanese university female students

    Hiroko Terui-Kohbata, Makiko Egawa, Kei Yura, Masayuki Yoshida

    Journal of Human Genetics   65 ( 7 ) 591 - 599  2020.07  [Refereed]  [International journal]

     View Summary

    BRCA1/2 genetic testing to use PARP inhibitor for breast cancer has a possibility of the "secondary finding" among the younger nonaffected family members of the patient, which turns them into at-risk for hereditary breast cancer. Proper understanding of the background of the hereditary cancer is now required for appropriate acceptance of the risk. Therefore, we investigated the level of knowledge and attitudes of younger women on hereditary breast cancer in Japan. Study subject was Japanese university women between 20 and 30 years of age, without medical history of breast cancer. We conducted the anonymous self-answering questionnaire to them. We received responses from 353 women. The levels of knowledge, awareness, and interest were relatively high. Women with a family history of breast cancer were less likely to undergo testing than women without (92.8% vs. 74.5%, p < 0.001). The rates of positive response toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was significantly high for medical majors compared with that for other majors (RRM: medical 71.6% vs. science 54.5% vs. humanities 53.8%, p = 0.008, RRSO: 35.4% vs. 36.3% vs. 48.4%, p = 0.027). Approximately half of respondents answered that they would hesitate to get married (45.3%) or to have children (55.4%), if they were a BRCA1/2 mutation carrier. The results may help to establish the methods for supporting the decision-making for reproduction of younger women who are unexpectedly labeled as being at-risk for HBOC.

    DOI PubMed

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    2
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  • Diversification of CpG-Island Promoters Revealed by Comparative Analysis Between Human and Rhesus Monkey Genomes

    Kei Yura

    Mammalian Genome    2020.07

    DOI

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    3
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  • Diversification of CpG-Island Promoters Revealed by Comparative Analysis Between Human and Rhesus Monkey Genomes

    Saki Aoto, Mayu Fushimi, Kei Yura, Kohji Okamura

    Mammalian Genome    2020.07  [Refereed]

    DOI

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    3
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  • 15
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  • The reliability and validity of the Japanese version of Revised Illness Perception Questionnaires for Healthy people (IPQ-RH-J)

    Kei Yura

    British Journal of Cancer Research    2020.04  [International journal]

  • Biophysics at Waseda University

    Kei Yura

    Biophysical Reviews   12 ( 2 ) 225 - 232  2020.04

     View Summary

    Biophysics in Waseda University was started in 1965 as one of the three key research areas that constitute the Physics Department. In the biophysics group, one theoretical lab and two experimental labs are now working on the cutting-edge themes on biophysics, disseminating the ideas and knowledge of biophysics to undergraduate and graduate students from the viewpoint of physics.

    DOI

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    4
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  • Biophysics at Waseda University

    Mitsunori Takano, Kei Yura, Taro Uyeda, Kenji Yasuda

    Biophysical Reviews   12 ( 2 ) 225 - 232  2020.04  [Refereed]

     View Summary

    Biophysics in Waseda University was started in 1965 as one of the three key research areas that constitute the Physics Department. In the biophysics group, one theoretical lab and two experimental labs are now working on the cutting-edge themes on biophysics, disseminating the ideas and knowledge of biophysics to undergraduate and graduate students from the viewpoint of physics.

    DOI

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    4
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  • Metagenome Sequences from the Environment of Diseased Otter Clams, Lutraria rhynchaena, from a Farm in Vietnam

    Yuki Kagaya, Ryuhei Minei, Ha T. T. Duong, Binh T. N. Le, Lua T. Dang, Trang T. H. Tran, Hoa T. Nguyen, Kengo Kinoshita, Kei Yura, Atsushi Ogura, Oanh T. P. Kim, Kenneth M. Stedman

    Microbiology Resource Announcements   9 ( 2 )  2020.01  [Refereed]

     View Summary

    © 2020 Kagaya et al. Otter clam farming in Vietnam has recently encountered difficulties due to swollen-siphon disease. Here, we report the metagenome sequences of microorganisms extracted from the siphon tissue of infected otter clams. The data comprised bacterial and viral sequences which likely include those derived from the disease-causing agent.

    DOI

    Scopus

    1
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  • A prospective compound screening contest identified broader inhibitors for Sirtuin 1

    Kei Yura

    Scientific Reports   9 ( 1 )  2019.12  [Refereed]

     View Summary

    <title>Abstract</title>Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using <italic>in silico</italic> methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.

    DOI

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    13
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  • Engineered Functional Recovery of Microbial Rhodopsin Without Retinal‐Binding Lysine

    Kei Yura

    Photochemistry and Photobiology    2019.09

    DOI

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    5
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  • Engineered Functional Recovery of Microbial Rhodopsin Without Retinal-Binding Lysine.

    Yamauchi Y, Konno M, Yamada D, Yura K, Inoue K, Béjà O, Kandori H

    Photochemistry and photobiology   95 ( 5 ) 1116 - 1121  2019.09  [Refereed]

    DOI PubMed J-GLOBAL

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  • Starfish Apaf-1 activates effector caspase-3/9 upon apoptosis of aged eggs

    Tamura, R., Takada, M., Sakaue, M., Yoshida, A., Ohi, S., Hirano, K., Hayakawa, T., Hirohashi, N., Yura, K., Chiba, K.

    Scientific Reports   8 ( 1 ) 1611 - 1611  2018  [Refereed]  [International journal]

     View Summary

    Caspase-3-related DEVDase activity is initiated upon apoptosis in unfertilized starfish eggs. In this study, we cloned a starfish procaspase-3 corresponding to mammalian effector caspase containing a CARD that is similar to the amino terminal CARD of mammalian capsase-9, and we named it procaspase-3/9. Recombinant procaspase-3/9 expressed at 15 °C was cleaved to form active caspase-3/9 which has DEVDase activity. Microinjection of the active caspase-3/9 into starfish oocytes/eggs induced apoptosis. An antibody against the recombinant protein recognized endogenous procaspase-3/9 in starfish oocytes, which was cleaved upon apoptosis in aged unfertilized eggs. These results indicate that caspase-3/9 is an effector caspase in starfish. To verify the mechanism of caspase-3/9 activation, we cloned starfish Apaf-1 containing a CARD, a NOD, and 11 WD40 repeat regions, and we named it sfApaf-1. Recombinant sfApaf-1 CARD interacts with recombinant caspase-3/9 CARD and with endogenous procaspase-3/9 in cell-free preparations made from starfish oocytes, causing the formation of active caspase-3/9. When the cell-free preparation without mitochondria was incubated with inactive recombinant procaspase-3/9 expressed at 37 °C, DEVDase activity increased and apoptosome-like complexes were formed in the high molecular weight fractions containing both sfApaf-1 and cleaved caspase-3/9. These results suggest that sfApaf-1 activation is not dependent on cytochrome c.

    DOI PubMed

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    20
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  • Synaptic transmission from subplate neurons controls radial migration of neocortical neurons

    Ohtaka-Maruyama, C., Okamoto, M., Endo, K., Oshima, M., Kaneko, N., Yura, K., Okado, H., Miyata, T., Maeda, N.

    Science   360 ( 6386 ) 313 - 317  2018  [Refereed]

     View Summary

    The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-D-aspartate receptor)-mediated synaptic transmission from subplate neurons to multipolar neurons induces themultipolar-to-bipolar transition, leading to a change inmigration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggested that transient synapses formed on early immature neurons regulate radialmigration.

    DOI PubMed

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    101
    Citation
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  • iMusta4SLC: Database for the structural property and variations of solute carrier transporters

    Akiko Higuchi, Naoki Nonaka, Kei Yura

    Biophysics and Physicobiology   15 ( 0 ) 94 - 103  2018  [Refereed]

    DOI PubMed

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    6
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  • Preface of Special Issue "Databases".

    Yura K

    Biophysics and physicobiology   15   86  2018  [Refereed]

    DOI PubMed

    Scopus

  • REFOLDdb: A new and sustainable gateway to experimental protocols for protein refolding

    Mizutani, H., Sugawara, H., Buckle, A.M., Sangawa, T., Miyazono, K.-I., Ohtsuka, J., Nagata, K., Shojima, T., Nosaki, S., Xu, Y., Wang, D., Hu, X., Tanokura, M., Yura, K.

    BMC Structural Biology   17 ( 1 ) 4  2017  [Refereed]

     View Summary

    Background: More than 7000 papers related to "protein refolding" have been published to date, with approximately 300 reports each year during the last decade. Whilst some of these papers provide experimental protocols for protein refolding, a survey in the structural life science communities showed a necessity for a comprehensive database for refolding techniques. We therefore have developed a new resource "REFOLDdb" that collects refolding techniques into a single, searchable repository to help researchers develop refolding protocols for proteins of interest.
    Results: We based our resource on the existing REFOLD database, which has not been updated since 2009. We redesigned the data format to be more concise, allowing consistent representations among data entries compared with the original REFOLD database. The remodeled data architecture enhances the search efficiency and improves the sustainability of the database. After an exhaustive literature search we added experimental refolding protocols from reports published 2009 to early 2017. In addition to this new data, we fully converted and integrated existing REFOLD data into our new resource. REFOLDdb contains 1877 entries as of March 17th, 2017, and is freely available at http://p4d-info.nig.ac.jp/refolddb/.
    Conclusion: REFOLDdb is a unique database for the life sciences research community, providing annotated information for designing new refolding protocols and customizing existing methodologies. We envisage that this resource will find wide utility across broad disciplines that rely on the production of pure, active, recombinant proteins. Furthermore, the database also provides a useful overview of the recent trends and statistics in refolding technology development.

    DOI PubMed

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    11
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  • Druggability analysis and prediction based on geometric distances between amino acid residues and protein surface pockets

    Makiko Miyoshi, Ayaka Kaneko, Takayuki Itoh, Kei Yura, Masahiro Takatsuka

    Proceedings - NICOGRAPH International 2016, NicoInt 2016     21 - 24  2016.09  [Refereed]

     View Summary

    Protein is the major component of the organism. A concave (pocket) on a protein surface is known to be thebest target for a drug to react. We previously presented astudy on distance analysis between pockets and amino acidresidue. We firstly identified pockets on the protein surfaceand then calculated distances between atoms of an amino acidresidue and the deepest points or the outer loops of the pockets. We extracted proteins which at least one of the pockets areclose to arbitrary pairs of amino acid residues, calculated theratios of druggable proteins, and visualized the distributionof the ratios as a colored matrix. We suggested from thevisualization results that particular pairs of amino acid residuesmay affect the druggability of the proteins in our previousstudy. This paper presents an extension of our study to explorethe relevance between druggability of proteins and distancesbetween a set of amino acid residues and protein surfacepockets. Our technique treats the pockets as 20-dimensionalvectors consisting of distances to each of amino acid residues, and applies GeodesicSOM with the set of the vectors. Sphericalmaps generated by GeodesicSOM are used to visualizationof distribution of the pockets in the 20-dimensional vectorspace, and estimation of druggability of proteins with the 20-dimensional vectors of the pockets.

    DOI

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  • Complete genome sequence of the mitochondrial DNA of the sparkling enope squid, Watasenia scintillans

    Hayashi, K., Kawai, Y.L., Yura, K., Yoshida, M.-A., Ogura, A., Hata, K., Nakabayashi, K., Okamura, K.

    Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis   27 ( 3 ) 1842 - 1843  2016  [Refereed]

     View Summary

    The sparkling enope squid, Watasenia scintillans, is a deep-sea mollusk inhabiting the western part of the Pacific Ocean. It has the peculiar ability to illuminate its body without the involvement of other organisms. In this study, we extracted the brain DNA from a single squid female caught in the Japan Sea and determined the complete genome sequence of its mitochondrial DNA using the Illumina sequencing platform. The circular sequence is 20,089 bp in length. Using the next-generation sequencing data, we also estimated the mean copy number of mitochondria per cell in the brain to be 108 by comparig the depths of the read data in the nuclear and mitochondrial genomes. The haploid genome size was calculated to be 4.78 Gb. Six heteroplasmy sites were also identified, together with their allele frequencies, in this individual. Our methodology is shown to be useful in mitochondrion-related studies.

    DOI PubMed

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    5
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  • Preface of Special Issue "Protein-Ligand Interactions".

    Yura K

    Biophysics and physicobiology   13   85 - 86  2016  [Refereed]

    DOI PubMed CiNii

    Scopus

  • Conformational shift in the closed state of GroEL induced by ATP-binding triggers a transition to the open state.

    Suzuki Y, Yura K

    Biophysics and physicobiology   13   127 - 134  2016  [Refereed]

     View Summary

    <p>We investigated the effect of ATP binding to GroEL and elucidated a role of ATP in the conformational change of GroEL. GroEL is a tetradecamer chaperonin that helps protein folding by undergoing a conformational change from a closed state to an open state. This conformational change requires ATP, but does not require the hydrolysis of the ATP. The following three types of conformations are crystalized and the atomic coordinates are available; closed state without ATP, closed state with ATP and open state with ADP. We conducted simulations of the conformational change using Elastic Network Model from the closed state without ATP targeting at the open state, and from the closed state with ATP targeting at the open state. The simulations emphasizing the lowest normal mode showed that the one started with the closed state with ATP, rather than the one without ATP, reached a conformation closer to the open state. This difference was mainly caused by the changes in the positions of residues in the initial structure rather than the changes in "connectivity" of residues within the subunit. Our results suggest that ATP should behave as an insulator to induce conformation population shift in the closed state to the conformation that has a pathway leading to the open state.</p>

    DOI PubMed CiNii

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    4
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  • VaProS: a database-integration approach for protein/genome information retrieval

    Gojobori, T., Ikeo, K., Katayama, Y., Kawabata, T., Kinjo, A.R., Kinoshita, K., Kwon, Y., Migita, O., Mizutani, H., Muraoka, M., Nagata, K., Omori, S., Sugawara, H., Yamada, D., Yura, K.

    Journal of Structural and Functional Genomics   17 ( 4 ) 69 - 81  2016  [Refereed]

     View Summary

    Life science research now heavily relies on all sorts of databases for genome sequences, transcription, protein three-dimensional (3D) structures, protein–protein interactions, phenotypes and so forth. The knowledge accumulated by all the omics research is so vast that a computer-aided search of data is now a prerequisite for starting a new study. In addition, a combinatory search throughout these databases has a chance to extract new ideas and new hypotheses that can be examined by wet-lab experiments. By virtually integrating the related databases on the Internet, we have built a new web application that facilitates life science researchers for retrieving experts’ knowledge stored in the databases and for building a new hypothesis of the research target. This web application, named VaProS, puts stress on the interconnection between the functional information of genome sequences and protein 3D structures, such as structural effect of the gene mutation. In this manuscript, we present the notion of VaProS, the databases and tools that can be accessed without any knowledge of database locations and data formats, and the power of search exemplified in quest of the molecular mechanisms of lysosomal storage disease. VaProS can be freely accessed at http://p4d-info.nig.ac.jp/vapros/.

    DOI PubMed

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    9
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  • Special issue: big data analyses in structural and functional genomics

    Yokoyama, S., Yura, K.

    Journal of Structural and Functional Genomics   17 ( 4 ) 67 - 67  2016  [Refereed]

    DOI PubMed

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    2
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  • Memorial Issue for Professor Nobuhiko Saitô.

    Yura K, Wako H

    Biophysics and physicobiology   13   243 - 243  2016  [Refereed]

    DOI PubMed CiNii

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  • Candidate key genes for low-salinity adaptation identified by RNA-seq comparison between closely related Ulva species in marine and brackish waters.

    Yuka Masakiyo, Atsushi Ogura, Kensuke Ichihara, Kei Yura, Satoshi Shimada

       2016  [Refereed]

  • Complete genome sequence of the mitochondrial DNA of the river lamprey, Lethenteron japonicum

    Kawai, Y.L., Yura, K., Shindo, M., Kusakabe, R., Hayashi, K., Hata, K., Nakabayashi, K., Okamura, K.

    Mitochondrial DNA   26 ( 6 ) 863 - 864  2015  [Refereed]

     View Summary

    Lampreys are eel-like jawless fishes evolutionarily positioned between invertebrates and vertebrates, and have been used as model organisms to explore vertebrate evolution. In this study we determined the complete genome sequence of the mitochondrial DNA of the Japanese river lamprey, Lethenteron japonicum, using next-generation sequencers. The sequence was 16,272 bp in length. The gene content and order were identical to those of the sea lamprey, Petromyzon marinus, which has been the reference among lamprey species. However, the sequence similarity was less than 90%, suggesting the need for the whole-genome sequencing of L. japonicum.

    DOI PubMed

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    2
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  • Distinct evolutionary rate in the eye field transcription factors found by estimation of ancestral protein structure

    Kamijyo, A., Yura, K., Ogura, A.

    Gene   555 ( 2 ) 73 - 79  2015  [Refereed]

     View Summary

    Eye-field transcription factors (EFTFs) are a set of genes that compose a regulatory network for eye development in animals, which are highly conserved among various animal phyla. To investigate the processes of conservation and diversification of the transcription factors for eye development, we examined the structural changes in the EFTF proteins by estimating the ancestral sequences with the available genome information. Among the different types of EFTFs, we selected otx2, tbx3, rx1, pax6, six3/6, Ihx2 and nr2e1 because they are highly conserved in bilaterian animals. We searched the genome sequences of representative animal phyla for EFTF protein sequences. With deduced ancestral sequences and three-dimensional structures of EFTFs, we traced the evolutionary changes in amino add residues and found that the DNA-binding domains were always more conserved than other regions, and that the other regions showed distinct evolutionary rates. The EFTF rx1, which resides at the pivotal part of the EFTF network, had a faster evolutionary rate than the others. These results indicated that the evolutionary rates of each protein in the EFTF network, which were expected to be consistent with each other to maintain the interactions in the network, were not constant among or within the factors, but rather, varied to a significant extent. (C) 2014 Published by Elsevier B.V.

    DOI PubMed

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    6
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  • Case study on the evolution of hetero-oligomer interfaces based on the differences in paralogous proteins

    Saki Aoto, Kei Yura

    Biophysics and Physicobiology   12 ( 0 ) 103 - 116  2015  [Refereed]

    DOI PubMed

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    2
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  • Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function

    Hori-Tanaka, Y., Yura, K., Takai-Igarashi, T., Tanaka, H.

    Steroids   96   81 - 88  2015  [Refereed]

     View Summary

    Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone. (C) 2015 Elsevier Inc. All rights reserved.

    DOI PubMed

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    4
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  • Structural and functional analyses of Barth syndrome-causing mutations and alternative splicing in the tafazzin acyltransferase domain

    Hijikata, A., Yura, K., Ohara, O., Go, M.

    Meta Gene   4   92 - 106  2015  [Refereed]

     View Summary

    Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS). Human tafazzin gene produces four distinct alternatively spliced transcripts. To understand the molecular mechanisms of tafazzin deficiency, we performed an atomic resolution analysis of the influence of the BTHS mutations and of alternative splicing on the structure and function of tafazzin. From the three-dimensional (3D) homology modeling of tafazzin, we identified candidate amino acid residues that contribute to cardiolipin binding and to mitochondrial membrane associations that facilitate acyl-transfer reactions. Primate specific exon 5, which is alternatively spliced, is predicted to correspond to an intrinsically unstructured region in the protein. We proposed that this region should change the substrate-binding affinity and/or contribute to primate-specific molecular interactions. Exon 7, another alternatively spliced exon, encodes a region forming a part of the putative substrate-binding cleft, suggesting that the gene products lacking exon 7 will lose their substrate-binding ability. We demonstrate a clear localization of the BTHS mutations at residues responsible for membrane association, substrate binding, and the conformational stability of tafazzin. These findings provide new insights into the function of defective tafazzin and the pathogenesis of BTHS at the level of protein 3D structure and the evolution of alternatively spliced exons in primates.

    DOI PubMed

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    16
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  • Biochemical analysis of phytolacca DOPA dioxygenase

    Takahashi, K., Yoshida, K., Yura, K., Ashihara, H., Sakuta, M.

    Natural Product Communications   10 ( 5 ) 717 - 719  2015  [Refereed]

     View Summary

    The biochemical analysis of Phytolacca americana DOPA dioxygenases (PaDOD1 and PaDOD2) was carried out. The recombinant protein of PaDOD1 catalyzed the conversion of DOPA to betalamic acid, whereas DOD activity was not detected in PaDOD2 in vitro. While the reported motif conserved in DODs from betalain-producing plants was found in PaDOD1, a single amino acid residue alteration was detected in PaDOD2. A mutated PaDOD1 protein with a change of 177 Asn to Gly showed reduced specific activity compared with PaDOD1, while DOPA dioxygenase activity was not observed for a mutated PaDOD2 protein which had its conserved motif replaced with that of PaDOD1. A three-dimensional (3D) structural model of PaDOD1 and PaDOD2 showed that the conserved motif in DODs was located in the N-terminal side of a loop, which was found close to the putative active site. The difference in stability of the loop may affect the enzymatic activity of PaDOD2.

    PubMed

  • Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel androgen receptor antagonists

    Inoue, K., Urushibara, K., Kanai, M., Yura, K., Fujii, S., Ishigami-Yuasa, M., Hashimoto, Y., Mori, S., Kawachi, E., Matsumura, M., Hirano, T., Kagechika, H., Tanatani, A.

    European Journal of Medicinal Chemistry   102   310 - 319  2015  [Refereed]

     View Summary

    The androgen receptor (AR) plays important roles in multiple physiological functions, including differentiation, growth, and maintenance of male reproductive organs, and also has effects on hair and skin. In this paper, we report the synthesis of nonsteroidal AR antagonists having a 4-benzyl-1-(2H)-phthalazinone skeleton. Among the synthesized compounds, 11c with two ortho-substituents on the phenyl group potently inhibited SC-3 cell proliferation (IC50: 0.18 mu M) and showed high wt AR-binding affinity (IC50: 10.9 mu M), comparable to that of hydroxyflutamide (3). Compound 11c also inhibited proliferation of LNCaP cells containing T877A-mutated AR. Docking study of 11c with the AR ligand-binding domain indicated that the benzyl group is important for the antagonism. These phthalazinone derivatives may be useful for investigating potential clinical applications of AR antagonists. (C) 2015 Elsevier Masson SAS. All rights reserved.

    DOI PubMed

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    25
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  • Structure of the microtubule-binding domain of flagellar dynein.

    Yusuke Kato, Toshiki Yagi, A Sarah Harris, Shin-ya Ohki, Kei Yura, Yousk? Shimizu, Shinya Honda, Ritsu Kamiya, A Stan Burgess, Masaru Tanokura

    Structure   Vol.22 ( No.11 ) 1628 - 1638  2014.11  [Refereed]

     View Summary

    Flagellar dyneins are essential microtubule motors in eukaryotes, as they drive the beating motions of cilia and flagella. Unlike myosin and kinesin motors, the track binding mechanism of dyneins and the regulation between the strong and weak binding states remain obscure. Here we report the solution structure of the microtubule-binding domain of flagellar dynein-c/DHC9 (dynein-c MTBD). The structure reveals a similar overall helix-rich fold to that of the MTBD of cytoplasmic dynein (cytoplasmic MTBD), but dynein-c MTBD has an additional flap, consisting of an antiparallel b sheet. The flap is positively charged and highly flexible. Despite the structural similarity to cytoplasmic MTBD, dynein-c MTBD shows only a small change in the microtubule- binding affinity depending on the registry change of coiled coil-sliding, whereby lacks the apparent strong binding state. The surface charge distribution of dynein-c MTBD also differs from that of cytoplasmic MTBD, which suggests a difference in the microtubule-binding mechanism.

    DOI PubMed

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    16
    Citation
    (Scopus)
  • Complete genome sequence of the mitochondrial DNA of the sparkling enope squid,Watasenia scintillans

    Keiko Hayashi, Yuri L. Kawai, Kei Yura, Masa-aki Yoshida, Atsushi Ogura, Kenichiro Hata, Kazuhiko Nakabayashi, Kohji Okamura

    Mitochondrial DNA     1 - 2  2014.10

    DOI

    Scopus

    5
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    (Scopus)
  • Complete genome sequence of the mitochondrial DNA of the sparkling enope squid, Watasenia scintillans.

    Hayashi K, Kawai YL, Yura K, Yoshida MA, Ogura A, Hata K, Nakabayashi K, Okamura K

    Mitochondrial DNA     1 - 2  2014.10  [Refereed]

    DOI PubMed

    Scopus

    5
    Citation
    (Scopus)
  • A visual analytics of geometric distances between amino acids and surface pockets of proteins

    Makiko Miyoshi, Ayaka Kaneko, Takayuki Itoh, Kei Yura

    Proceedings of the International Conference on Information Visualisation     164 - 169  2014.09  [Refereed]

     View Summary

    Protein is the major component of the organism. It has a unique three-dimensional structure determined by its amino acid sequence. A concave (pocket) on the surface of a protein is known to be the best target for a drug to react. We started analyzing how' drug ability' of proteins related to the location of amino acids in a pocket. For as tarter of the study, this paper presents a visualization tool for distance analysis between pockets and the amino acid residue. Provided that a protein surface is described by a triangular mesh, this tool first identifies pockets on the protein surface, specifies the deepest point and outer loops of the pocket, and calculates distances between atoms of an amino acid residue and the deepest point or the outer loops of the pocket. The tool then visualizes the statistics of the distance calculation results by poly line charts and the distribution by scatter plots. This paper proposes a biological interpretation of the visualization results.

    DOI

    Scopus

    1
    Citation
    (Scopus)
  • A Computational Study on the Role of a Methionine at a Discriminator Site of Cyclobutane-Pyrimidine-Dimer Photolyase

    Sato Ryuma, Kitoh-Nishioka Hirotaka, Kawatsu Tsutomu, Yura Kei, Ando Koji, Yamato Takahisa

    BIOPHYSICAL JOURNAL   106 ( 2 ) 690A  2014.01  [Refereed]

  • Structural insights of post-translational modification sites in the proteome of Thermus thermophilus

    Masui, R., Takahata, Y., Inoue, M., Iio, Y., Okanishi, H., Kim, K., Nakagawa, N., Yura, K., Kuramitsu, S.

    Journal of structural and functional genomics   15 ( 3 ) 137 - 151  2014  [Refereed]

    DOI PubMed

    Scopus

    4
    Citation
    (Scopus)
  • Cephalopod eye evolution was modulated by the acquisition of Pax-6 splicing variants

    Yoshida, M.-A., Yura, K., Ogura, A.

    Scientific Reports   4   4256  2014  [Refereed]

     View Summary

    Previous studies have reported that the developmental processes of vertebrate eyes are controlled by four Pax-6 splicing variants, each modulating different downstream genes, whereas those of insect eyes are controlled by duplicated Pax-6 genes. Cephalopods belong to the Protostomes but possess a camera-type eye similar to those in vertebrates. We examined Pax-6 variations in the squid and found five types of Pax-6 splicing variants but no duplication of the Pax-6 gene. In the five splicing variants, the splicing patterns were produced by the combination of two additional exons to the ortholog and one jettisoned exon containing most of the Homeobox domain (HD). These five variants show spatio-temporal patterns of gene expression during development in the squid. Our study suggests that cephalopods acquired Pax-6 splicing variants independent of those in vertebrates and that these variants were similarly utilized in the development of the squid eye.

    DOI PubMed

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    20
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    (Scopus)
  • Conformational behavior of flavin adenine dinucleotide: Conserved stereochemistry in bound and free states

    Kuppuraj, G., Kruise, D., Yura, K.

    Journal of Physical Chemistry B   118 ( 47 ) 13486 - 13497  2014  [Refereed]

     View Summary

    Metabolic enzymes utilize the cofactor flavin adenine dinucleotide (FAD) to catalyze essential biochemical reactions. Because these enzymes have been implicated in disease pathways, it will be necessary to target them via FAD-based structural analogues that can either activate/inhibit the enzymatic activity. To achieve this, it is important to explore the conformational space of FAD in the enzyme-bound and free states. Herein, we analyze X-ray crystallographic data of the enzyme-bound FAD conformations and sample conformations of the molecule in explicit water by molecular dynamics (MD) simulations. Enzyme-bound FAD conformations segregate into five distinct groups based on dihedral angle principal component analysis (PCA). A notable feature in the bound FADs is that the adenine base and isoalloxazine ring are oppositely oriented relative to the pyrophosphate axis characterized by near trans hypothetical dihedral angle ?V values. Not surprisingly, MD simulations in water show final compact but not perfectly stacked ring structures in FAD. Simulation data did not reveal noticeable changes in overall conformational dynamics of the dinucleotide in reduced and oxidized forms and in the presence and/or absence of ions. During unfoldingfolding dynamics, the riboflavin moiety is more flexible than the adenosine monophosphate group in the molecule. Conversely, the isoalloxazine ring is more stable than the variable adenine base. The pyrophosphate group depicts an unusually highly organized fluctuation illustrated by its dihedral angle distribution. Conformations sampled from enzymes and MD are quantified. The extent to which the protein shifts the distribution from the unbound state is discussed in terms of prevalent FAD shapes and dihedral angle population.

    DOI PubMed

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    17
    Citation
    (Scopus)
  • Structure of the Microtubule-Binding Domain of Flagellar Dynein

    Kato, Y.S., Yagi, T., Harris, S.A., Ohki, S.-Y., Yura, K., Shimizu, Y., Honda, S., Kamiya, R., Burgess, S.A., Tanokura, M.

    Structure   22 ( 11 ) 1628 - 1638  2014  [Refereed]

     View Summary

    Flagellar dyneins are essential microtubule motors in eukaryotes, as they drive the beating motions of cilia and flagella. Unlike myosin and kinesin motors, the track binding mechanism of dyneins and the regulation between the strong and weak binding states remain obscure. Here we report the solution structure of the microtubule-binding domain of flagellar dynein-c/DHC9 (dynein-c MTBD). The structure reveals a similar overall helix-rich fold to that of the MTBD of cytoplasmic dynein (cytoplasmic MTBD), but dynein-c MTBD has an additional flap, consisting of an antiparallel beta sheet. The flap is positively charged and highly flexible. Despite the structural similarity to cytoplasmic MTBD, dynein-c MTBD shows only a small change in the microtubule-binding affinity depending on the registry change of coiled coil-sliding, whereby lacks the apparent strong binding state. The surface charge distribution of dynein-c MTBD also differs from that of cytoplasmic MTBD, which suggests a difference in the microtubule-binding mechanism.

    DOI PubMed

    Scopus

    16
    Citation
    (Scopus)
  • 2P250 Theoretical study of the electron transfer reaction by DNA photolyase(18A. Photobiology:Vision & Photoreception,Poster)

    Sato Ryuma, Kitoh-Nishioka Hirotaka, Kawatsu Tsutomu, Yura Kei, Ando Koji, Yamato Takahisa

    Seibutsu Butsuri   54 ( 1 ) S236  2014

    DOI CiNii

  • Distinct conformation of ATP molecule in solution and on protein

    Kobayashi, E., Yura, K., Nagai, Y.

    Biophysics (Japan)   9   1 - 12  2013  [Refereed]

     View Summary

    Adenosine triphosphate (ATP) is a versatile molecule used mainly for energy and a phosphate source. The hydrolysis of γ phosphate initiates the reactions and these reactions almost always start when ATP binds to protein. Therefore, there should be a mechanism to prevent spontaneous hydrolysis reaction and a mechanism to lead ATP to a pure energy source or to a phosphate source. To address these questions, we extensively analyzed the effect of protein to ATP conformation based on the sampling of the ATP solution conformations obtained from molecular dynamics simulation and the sampling of ATP structures bound to protein found in a protein structure database. The comparison revealed mainly the following three points
    1) The ribose ring in ATP molecule, which puckers in many ways in solution, tends to assume either C2′ exo or C2′ endo when it binds to protein. 2) The adenine ring in ATP molecule, which takes open-book motion with the two ring structures, has two distinct structures when ATP binds to protein. 3) The glycosyl-bond and the bond between phosphate and the ribose have unique torsion angles, when ATP binds to protein. The combination of torsion angles found in protein-bound forms is under-represented in ATP molecule in water. These findings suggest that ATP-binding protein exerts forces on ATP molecule to assume a conformation that is rarely found in solution, and that this conformation change should be a trigger for the reactions on ATP molecule. © 2013 The Biophysical Society of Japan.

    DOI PubMed

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    18
    Citation
    (Scopus)
  • A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM<inf>1</inf> gangliosidosis

    Takai, T., Higaki, K., Aguilar-Moncayo, M., Mena-Barragán, T., Hirano, Y., Yura, K., Yu, L., Ninomiya, H., García-Moreno, M.I., Sakakibara, Y., Ohno, K., Nanba, E., Ortiz Mellet, C., García Fernández, J.M., Suzuki, Y.

    Molecular Therapy   21 ( 3 ) 526 - 532  2013  [Refereed]

     View Summary

    Lysosomal β-galactosidase (β-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use of small molecule ligands of β-Gal as pharmacological chaperones (PCs) for the treatment of GM1 gangliosidosis brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated the effect of bicyclic 1-deoxygalactonojirimycin (DGJ) derivative of the sp2-iminosugar type, namely 5N,6S-(N′-butyliminomethylidene)-6-thio-1- deoxygalactonojirimycin (6S-NBI-DGJ), as a novel PC for human mutant β-Gal. In vitro, 6S-NBI-DGJ had the ability to inhibit the activity of human β-Gal in a competitive manner and was able to protect this enzyme from heat-induced degradation. Computational analysis supported that the rigid glycone bicyclic core of 6S-NBI-DGJ binds to the active site of the enzyme, with the aglycone N′-butyl substituent, in a precise E-orientation, located at a hydrophobic region nearby. Chaperone potential profiling indicated significant increases of enzyme activity in 24 of 88 β-Gal mutants, including four common mutations. Finally, oral administration of 6S-NBI-DGJ ameliorated the brain pathology of GM1 gangliosidosis model mice. These results suggest that 6S-NBI-DGJ is a novel PC that may be effective on a broad range of β-Gal mutants. Copyright © 2013, The American Society of Gene &amp
    Cell Therapy.

    DOI PubMed

    Scopus

    67
    Citation
    (Scopus)
  • CoDP: Predicting the impact of unclassified genetic variants in MSH6 by the combination of different properties of the protein

    Terui, H., Akagi, K., Kawame, H., Yura, K.

    Journal of Biomedical Science   20 ( 1 ) 25  2013  [Refereed]

     View Summary

    Background: Lynch syndrome is a hereditary cancer predisposition syndrome caused by a mutation in one of the DNA mismatch repair (MMR) genes. About 24% of the mutations identified in Lynch syndrome are missense substitutions and the frequency of missense variants in MSH6 is the highest amongst these MMR genes. Because of this high frequency, the genetic testing was not effectively used in MSH6 so far. We, therefore, developed CoDP (Combination of the Different Properties), a bioinformatics tool to predict the impact of missense variants in MSH6.
    Methods: We integrated the prediction results of three methods, namely MAPP, PolyPhen-2 and SIFT. Two other structural properties, namely solvent accessibility and the change in the number of heavy atoms of amino acids in the MSH6 protein, were further combined explicitly. MSH6 germline missense variants classified by their associated clinical and molecular data were used to fit the parameters for the logistic regression model and to assess the prediction. The performance of CoDP was compared with those of other conventional tools, namely MAPP, SIFT, PolyPhen-2 and PON-MMR.
    Results: A total of 294 germline missense variants were collected from the variant databases and literature. Of them, 34 variants were available for the parameter training and the prediction performance test. We integrated the prediction results of MAPP, PolyPhen-2 and SIFT, and two other structural properties, namely solvent accessibility and the change in the number of heavy atoms of amino acids in the MSH6 protein, were further combined explicitly. Variants data classified by their associated clinical and molecular data were used to fit the parameters for the logistic regression model and to assess the prediction. The values of the positive predictive value (PPV), the negative predictive value (NPV), sensitivity, specificity and accuracy of the tools were compared on the whole data set. PPV of CoDP was 93.3% (14/15), NPV was 94.7% (18/19), specificity was 94.7% (18/19), sensitivity was 93.3% (14/15) and accuracy was 94.1% (32/34). Area under the curve of CoDP was 0.954, that of MAPP for MSH6 was 0.919, of SIFT was 0.864 and of PolyPhen-2 HumVar was 0.819. The power to distinguish between pathogenic and non-pathogenic variants of these methods was tested by Wilcoxon rank sum test (p &lt; 8.9 x 10(-6) for CoDP, p &lt; 3.3 x 10(-5) for MAPP, p &lt; 3.1 x 10(-4) for SIFT and p &lt; 1.2 x 10(-3) for PolyPhen-2 HumVar), and CoDP was shown to outperform other conventional methods.
    Conclusion: In this paper, we provide a human curated data set for MSH6 missense variants, and CoDP, the prediction tool, which achieved better accuracy for predicting the impact of missense variants in MSH6 than any other known tools. CoDP is available at http://cib.cf.ocha.ac.jp/CoDP/.

    DOI PubMed

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    14
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  • Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA

    Hoshina, S., Yura, K., Teranishi, H., Kiyasu, N., Tominaga, A., Kadoma, H., Nakatsuka, A., Kunichika, T., Obuse, C., Waga, S.

    Journal of Biological Chemistry   288 ( 42 ) 30161 - 30171  2013  [Refereed]

     View Summary

    Background: ORC binds to replication origins, but human ORC does not exhibit apparent sequence-specificity. Results: G-quadruplex (G4)-preferable RNA or single-stranded DNA competes for DNA binding of ORC. Conclusion: HumanORCbinds preferentially toRNAand single-strandedDNAthat form G4, and the certain domain in ORC1 is involved in this binding. Significance: This ability may correlate with the G4-formable motif in human replication origins. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

    DOI PubMed

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    83
    Citation
    (Scopus)
  • [Combinatorial approach of molecular dynamics simulations and database analyses for the studies of protein structure and function].

    Yamato, T., Yura, K.

    Seikagaku. The Journal of Japanese Biochemical Society   85 ( 8 ) 646 - 655  2013  [Refereed]

    PubMed

  • Molecular and clinical characteristics of MSH6 germline variants detected in colorectal cancer patients

    Terui, H., Tachikawa, T., Kakuta, M., Nishimura, Y., Yatsuoka, T., Yamaguchi, K., Yura, K., Akagi, K.

    Oncology Reports   30 ( 6 ) 2909 - 2916  2013  [Refereed]

     View Summary

    The MSH6 gene is one of the mismatch repair genes involved in Lynch syndrome and its mutations account for 10-20% of Lynch syndrome. Although previous studies suggested that the difference of the geographical region affects the clinical phenotype of Lynch syndrome, there has been no report on the detailed features of Japanese Lynch syndrome patients carrying an MSH6 mutation. The aim of the present study was to investigate the clinical and molecular features of MSH6 mutation carriers in Japan. Surgically resected 1720 colorectal carcinoma specimens were screened by microsatellite instability (MSI) testing and the MSI-high cases were subjected to a germline mutation analysis of the mismatch repair genes MLH1, MSH2 and MSH6. We investigated the clinical and molecular features of the MSH6 variants, such as the family cancer history, pathological findings, immunohistochemistry, methylation status of the MLH1 promoter and BRAF mutation in the colorectal tumor. Furthermore, the impact of the missense variants on MSH6 protein was predicted by using in silico tools. We identified nine novel pathogenic mutations and eight unclassified missense variants. Among the eight missense variants, three were suspected pathogenic by in silico analysis. We also found that most colorectal cancers in the MSH6 mutation carrier were diagnosed after the age of 50 and were localized distally. Furthermore, the mean age at diagnosis of endometrial cancer in Japanese MSH6 mutation carriers (49.2 years) was earlier than previous reports from Western countries (56.5 years). These results may improve the surveillance program for Japanese MSH6 mutation carriers.

    DOI PubMed

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    18
    Citation
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  • A scatterplot-based visual analytics tool for protein pocket properties

    Makiko Miyoshi, Ayaka Kaneko, Takayuki Itoh, Kei Yura

    Proceedings - 2013 International Conference on Cyberworlds, CW 2013     379  2013  [Refereed]

     View Summary

    Protein is the major component of the organism. A hole (pocket) on the surface of a protein is known to be the best target for a drug to react. We started analyzing how 'drug ability' of proteins related to the locations amino acids in a pocket. This poster presents a visualization tool for a distance distribution analysis between two types of amino acids in a pocket and proposes the biological interpretation of the visualization results. © 2013 IEEE.

    DOI

    Scopus

  • Early Research in Biophysics Award : Report on the Eighth Award Nomination Process

    YURA Kei

    Seibutsu Butsuri   52 ( 6 ) 304 - 305  2012.11

    DOI CiNii

  • 境界にいることを楽しもう

    由良 敬

    生物物理   52 ( 3 ) 123 - 123  2012.05

    DOI CiNii

  • 1I1412 Database analysis of the degree of protein conformational changes in RNA-protein interactions(Bioinformatics & Bioengineering,Oral Presentation,The 50th Annual Meeting of the Biophysical Society of Japan)

    Kubota Chihiro, Yura Kei

    Seibutsu Butsuri   52   S35  2012

    DOI CiNii

  • Tuning glycosidase inhibition through aglycone interactions: Pharmacological chaperones for Fabry disease and GM <inf>1</inf> gangliosidosis

    Aguilar-Moncayo, M., Takai, T., Higaki, K., Mena-Barragán, T., Hirano, Y., Yura, K., Li, L., Yu, Y., Ninomiya, H., García-Moreno, M.I., Ishii, S., Sakakibara, Y., Ohno, K., Nanba, E., Ortiz Mellet, C., García Fernández, J.M., Suzuki, Y.

    Chemical Communications   48 ( 52 ) 6514 - 6516  2012  [Refereed]

     View Summary

    Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions with conformationally locked sp 2-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- and β-Gal associated with Fabry disease and GM 1 gangliosidosis. © 2012 The Royal Society of Chemistry.

    DOI PubMed

    Scopus

    56
    Citation
    (Scopus)
  • Birth of "Promenade along Protein 3D Structures"

    YURA Kei

    Seibutsu Butsuri   51 ( 3 ) 144 - 145  2011.05

    DOI CiNii

  • Revisiting gap locations in amino acid sequence alignments and a proposal for a method to improve them by introducing solvent accessibility

    Hijikata, A., Yura, K., Noguti, T., Go, M.

    Proteins: Structure, Function and Bioinformatics   79 ( 6 ) 1868 - 1877  2011  [Refereed]

     View Summary

    In comparative modeling, the quality of amino acid sequence alignment still constitutes a major bottleneck in the generation of high quality models of protein three-dimensional (3D) structures. Substantial efforts have been made to improve alignment quality by revising the substitution matrix, introducing multiple sequences, replacing dynamic programming with hidden Markov models, and incorporating 3D structure information. Improvements in the gap penalty have not been a major focus, however, following the development of the affine gap penalty and of the secondary structure dependent gap penalty. We revisited the correlation between protein 3D structure and gap location in a large protein 3D structure data set, and found that the frequency of gap locations approximated to an exponential function of the solvent accessibility of the inserted residues. The nonlinearity of the gap frequency as a function of accessibility corresponded well to the relationship between residue mutation pattern and residue accessibility. By introducing this relationship into the gap penalty calculation for pairwise alignment between template and target amino acid sequences, we were able to obtain a sequence alignment much closer to the structural alignment. The quality of the alignments was substantially improved on a pair of sequences with identity in the "twi-light zone&apos;&apos; between 20 and 40%. The relocation of gaps by our new method made a significant improvement in comparative modeling, exemplified here by the Bacillus subtilis yitF protein. The method was implemented in a computer program, ALAdeGAP (ALignment with Accessibility dependent GAp Penalty), which is available at http://cib.cf.ocha.ac.jp/target_protein/. Proteins 2011; 79:1868-1877. (C) 2011 Wiley-Liss, Inc.

    DOI PubMed

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    22
    Citation
    (Scopus)
  • 1E1424 A method to improve homology modeling of proteins : Insertion-deletion frequency depending on surface accessibility(Genome biology, Bioinformatics,The 49th Annual Meeting of the Biophysical Society of Japan)

    Hijikata Atsushi, Yura Kei, Go Mitiko

    Seibutsu Butsuri   51   S40  2011

    DOI CiNii

  • タンパク質構造から機能を推定する : 構造バイオインフォマティクス

    由良 敬

    化学と生物   48 ( 1 ) 43 - 50  2010.01

     View Summary

    「タンパク質の構造を決める」シリーズの第6回では,決定されたタンパク質の立体構造から機能を推定する方法について概観する.過去5回の解説では,タンパク質構造解析法の最前線が紹介されてきた.機能がすでによくわかっているタンパク質の立体構造を決定すると,そのタンパク質がどのように機能しているのかを化学的に理解することができるようになる.特に酵素の場合は,反応機構の詳細を明らかにできる.しかし近年,タンパク質の機能解析において,別のアプローチが登場してきた.ある生物種のゲノム全塩基配列を決定できるようになった結果,生物は新規のタンパク質をたくさんもっていることが明らかになった.このタンパク質がどのような機能をもっているのかを知るための手段のひとつとして,そのタンパク質の立体構造決定も行なわれている(構造ゲノミクス).新規タンパク質の機能を立体構造から推定しようという試みである.これは今までにない新しいアプローチであり,立体構造から機能を推定する問題として,構造バイオインフォマティクス研究者による挑戦が続いている.ここでは,タンパク質の立体構造からどのようにして機能を推定するのか,そしてどこに困難な点があるのかを紹介する.

    DOI CiNii

  • 2SB1350 The interwinding nature of protein-protein interfaces and its implication for protein complex formation(2SB Intrinsically Disordered Proteins:Structure,Property and Function,The 48th Annual Meeting of the Biophysical Society of Japan)

    Yura Kei, Hayward Steven

    Seibutsu Butsuri   50 ( 2 ) S9  2010

    DOI CiNii

  • [Structural bioinformatics].

    Yura, K., Shionyu, M., Toh, H.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   54 ( 12 Suppl ) 1535 - 1541  2009  [Refereed]

    PubMed

  • The interwinding nature of protein protein interfaces and its implication for protein complex formation

    Yura, K., Hayward, S.

    Bioinformatics   25 ( 23 ) 3108 - 3113  2009  [Refereed]

     View Summary

    Motivation: Structural features at protein-protein interfaces can be studied to understand protein-protein interactions. It was noticed that in a dataset of 45 multimeric proteins the interface could either be described as. at against. at or protruding/interwound. In the latter, residues within one chain were surrounded by those in other chains, whereas in the former they were not.
    Results: A simple method was developed that could distinguish between these two types with results that matched those made by a human annotator. Applying this automatic method to a large dataset of 888 structures, chains at interfaces were categorized as non-surrounded or surrounded. It was found that the surrounded set had a significantly lower folding tendency using a sequence based measure, than the non-surrounded set. This suggests that before complexation, surrounded chains are relatively unstable and may be involved in &apos;fly-casting&apos;. This is supported by the finding that terminal regions are overrepresented in the surrounded set.

    DOI PubMed

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    16
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    (Scopus)
  • RESOPS: A database for analyzing the correspondence of rna editing sites to protein three-dimensional structures

    Yura, K., Sulaiman, S., Hatta, Y., Shionyu, M., Go, M.

    Plant and Cell Physiology   50 ( 11 ) 1865 - 1873  2009  [Refereed]

     View Summary

    Transcripts from mitochondrial and chloroplast DNA of land plants often undergo cytidine to uridine conversion-type RNA editing events. RESOPS is a newly built database that specializes in displaying RNA editing sites of land plant organelles on protein three-dimensional (3D) structures to help elucidate the mechanisms of RNA editing for gene expression regulation. RESOPS contains the following information: unedited and edited cDNA sequences with notes for the target nucleotides of RNA editing, conceptual translation from the edited cDNA sequence in pseudo-UniProt format, a list of proteins under the influence of RNA editing, multiple amino acid sequence alignments of edited proteins, the location of amino acid residues coded by codons under the influence of RNA editing in protein 3D structures and the statistics of biased distributions of the edited residues with respect to protein structures. Most of the data processing procedures are automated; hence, it is easy to keep abreast of updated genome and protein 3D structural data. In the RESOPS database, we clarified that the locations of residues switched by RNA editing are significantly biased to protein structural cores. The integration of different types of data in the database also help advance the understanding of RNA editing mechanisms. RESOPS is accessible at http://cib.cf.ocha.ac.jp/RNAEDITING/.

    DOI PubMed

    Scopus

    21
    Citation
    (Scopus)
  • Identification of Functional Residues of DNA Photolyase by Biophysical Computation and Bioinformatics

    Takahisa YAMATO, Hirotaka NISHIOKA, Kei YURA

    Seibutsu Butsuri   49 ( 4 ) 196 - 197  2009  [Refereed]

    DOI CiNii

  • ColiSNP database server mapping nsSNPs on protein structures

    Kono, H., Yuasa, T., Nishiue, S., Yura, K.

    Nucleic Acids Research   36 ( SUPPL. 1 ) D409 - D413  2008  [Refereed]

     View Summary

    We have developed coliSNP, a database server (http://yayoi.kansai.jaea.go.jp/colisnp) that maps non-synonymous single nucleotide polymorphisms (nsSNPs) on the three-dimensional (3D) structure of proteins. Once a week, the SNP data from the dbSNP database and the protein structure data from the Protein Data Bank (PDB) are downloaded, and the correspondence of the two data sets is automatically tabulated in the coliSNP database. Given an amino acid sequence, protein name or PDB ID, the server will immediately provide known nsSNP information, including the amino acid mutation caused by the nsSNP, the solvent accessibility, the secondary structure and the flanking residues of the mutated residue in a single page. The position of the nsSNP within the amino acid sequence and on the 3D structure of the protein can also be observed. The database provides key information with which to judge whether an observed nsSNP critically affects protein function and/or stability. As far as we know, this is the only web-based nsSNP database that automatically compiles SNP and protein information in a concise manner.

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    19
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    (Scopus)
  • Discrimination of class i cyclobutane pyrimidine dimer photolyase from blue light photoreceptors by single methionine residue

    Miyazawa, Y., Nishioka, H., Yura, K., Yamato, T.

    Biophysical Journal   94 ( 6 ) 2194 - 2203  2008  [Refereed]

     View Summary

    DNA photolyase recognizes ultraviolet-damaged DNA and breaks improperly formed covalent bonds within the cyclobutane pyrimidine dimer by a light-activated electron transfer reaction between the flavin adenine dinucleotide, the electron donor, and cyclobutane pyrimidine dinner, the electron acceptor. Theoretical analysis of the electron-tunneling pathways of the DNA photolyase derived from Anacystis nidulans can reveal the active role of the protein environment in the electron transfer reaction. Here, we report the unexpectedly important role of the single methionine residue, Met-353, where busy trafficking of electron-tunneling currents is observed. The amino acid conservation pattern of Met-353 in the homologous sequences perfectly correlates with experimentally verified annotation as photolyases. The bioinformatics sequence analysis also suggests that the residue plays a pivotal role in biological function. Consistent findings from different disciplines of computational biology strongly suggest the pivotal role of Met-353 in the biological function of DNA photolyase.

    DOI PubMed

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    21
    Citation
    (Scopus)
  • The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts

    Yamasaki, C., Murakami, K., Fujii, Y., Sato, Y., Harada, E., Takeda, J.-I., Taniya, T., Sakate, R., Kikugawa, S., Shimada, M., Tanino, M., Koyanagi, K.O., Barrero, R.A., Gough, C., Chun, H.-W., Habara, T., Hanaoka, H., Hayakawa, Y., Hilton, P.B., Kaneko, Y., Kanno, M., Kawahara, Y., Kawamura, T., Matsuya, A., Nagata, N., Nishikata, K., Noda, A.O., Nurimoto, S., Saichi, N., Sakai, H., Sanbonmatsu, R., Shiba, R., Suzuki, M., Takabayashi, K., Takahashi, A., Tamura, T., Tanaka, M., Tanaka, S., Todokoro, F., Yamaguchi, K., Yamamoto, N., Okido, T., Mashima, J., Hashizume, A., Jin, L., Lee, K.-B., Lin, Y.-C., Nozaki, A., Sakai, K., Tada, M., Miyazaki, S., Makino, T., Ohyanagi, H., Osato, N., Tanaka, N., Suzuki, Y., Ikeo, K., Saitou, N., Sugawara, H., O'Donovan, C., Kulikova, T., Whitfield, E., Halligan, B., Shimoyama, M., Twigger, S., Yura, K., Kimura, K., Yasuda, T., Nishikawa, T., Akiyama, Y., Motono, C., Mukai, Y., Nagasaki, H., Suwa, M., Horton, P., Kikuno, R., Ohara, O., Lancet, D., Eveno, E., Graudens, E., Imbeaud, S., Debily, M.A., Hayashizaki, Y., Amid, C., Han, M., Osanger, A., Endo, T., Thomas, M.A., Hirakawa, M., Makalowski, W., Nakao, M., Kim, N.-S., Yoo, H.-S., De Souza, S.J., De Fatima Bonaldo, M., Niimura, Y., Kuryshev, V., Schupp, I., Wiemann, S., Bellgard, M., Shionyu, M., Jia, L., Thierry-Mieg, D., Thierry-Mieg, J., Wagner, L., Zhang, Q., Go, M., Minoshima, S., Ohtsubo, M., Hanada, K., Tonellato, P., Isogai, T., Zhang, J., Lenhard, B., Kim, S., Chen, Z., Hinz, U., Estreicher, A., Nakai, K., Makalowska, I., Hide, W., Tiffin, N., Wilming, L., Chakraborty, R., Soares, M.B., Chiusano, M.L., Suzuki, Y., Auffray, C., Yamaguchi-Kabata, Y., Itoh, T., Hishiki, T., Fukuchi, S., Nishikawa, K., Sugano, S., Nomura, N., Tateno, Y., Imanishi, T., Gojobori, T.

    Nucleic Acids Research   36 ( SUPPL. 1 ) D793 - D799  2008  [Refereed]

     View Summary

    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, proteinprotein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.

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    58
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  • Key interactions in integrin ectodomain responsible for global conformational change detected by elastic network normal-mode analysis

    Matsumoto, A., Kamata, T., Takagi, J., Iwasaki, K., Yura, K.

    Biophysical Journal   95 ( 6 ) 2895 - 2908  2008  [Refereed]

     View Summary

    Integrin, a membrane protein with a huge extracellular domain, participates in cell-cell and cell-extracellular-matrix interactions for metazoan. A group of integrins is known to perform a large-scale structural change when the protein is activated, but the activation mechanism and generality of the conformational change remain to be elucidated. We performed normal-mode analysis of the elastic network model on integrin alpha(V)beta(3) ectodomain in the bent form and identified key residues that influenced molecular motions. Iterative normal-mode calculations demonstrated that the specific nonbonded interactions involving the key residues work as a snap to keep integrin in the bent form. The importance of the key residues for the conformational change was further verified by mutation experiments, in which integrin alpha(IIb)beta(3) was used. The conservation pattern of amino acid residues among the integrin family showed that the characteristic pattern of residues seen around these key residues is found in the limited groups of integrin beta-chains. This conservation pattern suggests that the molecular mechanism of the conformational change relying on the interactions found in integrin alpha(V)beta(3) is unique to the limited types of integrins.

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    20
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  • Correlation between amino acid residues converted by RNA editing and functional residues in protein three-dimensional structures in plant organelles

    Yura, K., Go, M.

    BMC Plant Biology   8   79  2008  [Refereed]

     View Summary

    Background: In plant organelles, specific messenger RNAs (mRNAs) are subjected to conversion editing, a process that often converts the first or second nucleotide of a codon and hence the encoded amino acid. No systematic patterns in converted sites were found on mRNAs, and the converted sites rarely encoded residues located at the active sites of proteins. The role and origin of RNA editing in plant organelles remain to be elucidated.
    Results: Here we study the relationship between amino acid residues encoded by edited codons and the structural characteristics of these residues within proteins, e. g., in protein-protein interfaces, elements of secondary structure, or protein structural cores. We find that the residues encoded by edited codons are significantly biased toward involvement in helices and protein structural cores. RNA editing can convert codons for hydrophilic to hydrophobic amino acids. Hence, only the edited form of an mRNA can be translated into a polypeptide with helix-preferring and core-forming residues at the appropriate positions, which is often required for a protein to form a functional three-dimensional (3D) structure.
    Conclusion: We have performed a novel analysis of the location of residues affected by RNA editing in proteins in plant organelles. This study documents that RNA editing sites are often found in positions important for 3D structure formation. Without RNA editing, protein folding will not occur properly, thus affecting gene expression. We suggest that RNA editing may have conferring evolutionary advantage by acting as a mechanism to reduce susceptibility to DNA damage by allowing the increase in GC content in DNA while maintaining RNA codons essential to encode residues required for protein folding and activity.

    DOI PubMed

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    34
    Citation
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  • Characteristics and prediction of rna editing sites in transcripts of the moss takakia lepidozioides chloroplast

    Yura, K., Miyata, Y., Arikawa, T., Higuchi, M., Sugita, M.

    DNA Research   15 ( 5 ) 309 - 321  2008  [Refereed]

     View Summary

    RNA editing in land plant organelles is a process primarily involving the conversion of cytidine to uridine in pre-mRNAs. The process is required for gene expression in plant organelles, because this conversion alters the encoded amino acid residues and improves the sequence identity to homologous proteins. A recent study uncovered that proteins encoded in the nuclear genome are essential for editing site recognition in chloroplasts; the mechanisms by which this recognition occurs remain unclear. To understand these mechanisms, we determined the genomic and cDNA sequences of moss Takakia lepidozioides chloroplast genes, then computationally analyzed the sequences within -30 to +10 nucleotides of RNA editing sites (neighbor sequences) likely to be recognized by trans-factors. As the T lepidozioides chloroplast has many RNA editing sites, the analysis of these sequences provides a unique opportunity to perform statistical analyses of chloroplast RNA editing sites. We divided the 302 obtained neighbor sequences into eight groups based on sequence similarity to identify group-specific patterns. The patterns were then applied to predict novel RNA editing sites in T. lepidozioides transcripts; similar to 60% of these predicted sites are true editing sites. The success of this prediction algorithm suggests that the obtained patterns are indicative of key sites recognized by trans-factors around editing sites of T. lepidozioides chloroplast genes.

    DOI PubMed

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    12
    Citation
    (Scopus)
  • A trial to predict interactions between proteins and biomolecules based on their three-dimensional structures

    Yura, K.

    Yakugaku Zasshi   128 ( 11 ) 1547 - 1555  2008  [Refereed]

     View Summary

    A vast amount of DNA sequence data, protein three-dimensional (3D) structure data, and RNA expression data have been produced by the efforts of genome sequencing, structural genomics, and omics projects, and we are at the stage where comprehensive views of cell activity and molecular mechanisms of life can be deduced. But in reality, we are inundated with massive amounts of data and are still in the process of finding ways to fully utilize the data. In this report, I would like to present our observations on the growth of protein 3D structure data and our effort to deduce the functions from the 3D structures. We found that the 3D structure of quite a high proportion of proteins derived from genome sequences can be now predicted and methods to predict the functions from 3D structures are in high demand. The methods we have developed can be used to predict some functions, namely RNA and ligand interfaces, based on those 3D structures and DNA sequences with relatively high accuracy. The methods enable predictions that are accurate enough to help with deducing the atomic structures of the complexes.

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  • Prediction of Molecular Interactions from 3D-Structures: From Small Ligands to Large Protein Complexes

    Kinoshita, K., Kono, H., Yura, K.

    Prediction of Protein Structures, Functions, and Interactions     159 - 186  2008  [Refereed]

    DOI

    Scopus

    1
    Citation
    (Scopus)
  • BAAQ: An infrastructure for application integration and knowledge discovery in bioinformatics

    Gong, X., Nakamura, K., Yu, H., Yura, K., Go, N.

    IEEE Transactions on Information Technology in Biomedicine   11 ( 4 ) 428 - 434  2007  [Refereed]

     View Summary

    The emerging grid computing technologies enable bioinformatics scientists to conduct their researches in a virtual laboratory, in which they share public databases, computational tools as well as their analysis workflows. However, the development of grid applications is still a nightmare for general bioinformatics scientists, due to the lack of grid programming environments, standards and high-level services. Here, we present a system, which we named Bioinformatics: Ask Any Questions (BAAQ), to automate this development procedure as much as possible. BAAQ allows scientists to store and manage remote biological data and programs, to build analysis workflows that integrate these resources seam-lessly, and to discover knowledge from available resources. This paper addresses two issues in building grid applications in bioinformatics: how to smoothly compose an analysis workflow using heterogeneous resources and how to efficiently discover and re-use available resources in the grid community. Correspondingly an intelligent grid programming environment and an active solution recommendation service are proposed. Finally, we present a case study applying BAAQ to a bioinformatics problem.

    DOI PubMed

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    5
    Citation
    (Scopus)
  • 1P253 Multiple protein docking guided by low-resolution image of complex using Gaussian mixture model under the symmetric constraint(Bioinformatics-structural genomics,Poster Presentations)

    Kawabata Takeshi, Yura Kei

    Seibutsu Butsuri   47   S86  2007

    DOI CiNii

  • 1P128 Molecular dynamics simulation of the 70S ribosome and nascent polypeptide passing through the exit tunnel(Nucleic acid,Poster Presentations)

    Ishida Hisashi, Yura Kei

    Seibutsu Butsuri   47   S55  2007

    DOI CiNii

  • 1P043 Snap residues of integrin activation identified by elastic network normal mode analysis(Proteins-functions,Poster Presentations)

    Matsumoto Atsushi, Kamata Tetsuji, Takagi Junichi, Iwasaki Kenji, Yura Kei

    Seibutsu Butsuri   47   S34  2007

    DOI CiNii

  • Contribution of computational biology and structural genomics to understand genome and transcriptome

    Mitiko Go, Kei Yura, Masafumi Shionyu

    FRONTIERS OF COMPUTATIONAL SCIENCE     75 - +  2007  [Refereed]

     View Summary

    Genome sequencing and structural genomics projects are both proceeded to gain a new perspective of life, that is global views on mechanisms of life with comprehensive and unbiased fashion. We now have genome sequences of human and other species, and are going to have a three-dimensional structure of whole proteins. Those massive pieces of information can only be deciphered with collaboration of computational biology. In this paper, we will discuss the amount of data we have at the moment and one of the new views on mechanisms of cellular function regulation obtained based on the computational analyses of those data.

  • 1P194 Multiple protein docking guided by low-resolution image of complex using Gaussian mixture model(6. Macromolecular assembly,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)

    Kawabata Takeshi, Yura Kei

    Seibutsu Butsuri   46 ( 2 ) S195  2006

    DOI CiNii

  • 2P304 Structure-based bioinformatics analyses of protein-RNA interface toward developing a computational method to predict protein-RNA interface

    Kim Oanh, Yura K., Go N.

    Seibutsu Butsuri   45   S195  2005

    DOI CiNii

  • 3P006 Fast Fitting Calculation of Low Resolution Protein Structures using Gaussian Mixture Model

    Kawabata T., Yuta K., Go N.

    Seibutsu Butsuri   45   S205  2005

    DOI CiNii

  • Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates

    OTP Kim, K Yura, N Gob, T Harumoto

    JOURNAL OF EUKARYOTIC MICROBIOLOGY   51 ( 2 ) 227 - 233  2004.03  [Refereed]

     View Summary

    We have cloned, sequenced, and characterized cDNA of actins from five ciliate species of three different classes of the phylum Ciliophora: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma japonicum, Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Loxodes striatus uses UGA as the stop codon and has numerous in-frame UAA and UAG, which are translated into glutamine. The other four species use UAA as the stop codon and have no in-frame UAG nor UGA. The putative amino acid sequences of the newly determined actin genes were found to be highly divergent as expected from previous findings of other ciliate actins. These sequences were also highly divergent from other ciliate actins, indicating that actin genes are highly diverse even within the phylum Ciliophora. Phylogenetic analysis showed high evolutionary rate of ciliate actins. Our results suggest that the evolutionary rate was accelerated because of the differences in molecular interactions.

    DOI PubMed

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    13
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  • Het-PDB Navi.: A Database for Protein-Small Molecule Interactions

    Yamaguchi, A., Iida, K., Matsui, N., Tomoda, S., Yura, K., Go, M.

    Journal of Biochemistry   135 ( 1 ) 79 - 84  2004  [Refereed]

     View Summary

    The genomes of more than 100 species have been sequenced, and the biological functions of encoded proteins are now actively being researched. Protein function is based on interactions between proteins and other molecules. One approach to assuming protein function based on genomic sequence is to predict interactions between an encoded protein and other molecules. As a data source for such predictions, knowledge regarding known protein-small molecule interactions needs to be compiled. We have, therefore, surveyed interactions between proteins and other molecules in Protein Data Bank (PDB), the protein three-dimensional (3D) structure database. Among 20,685 entries in PDB (April, 2003), 4,189 types of small molecules were found to interact with proteins. Biologically relevant small molecules most often found in PDB were metal ions, such as calcium, zinc, and magnesium. Sugars and nucleotides were the next most common. These molecules are known to act as cofactors for enzymes and/or stabilizers of proteins. In each case of interactions between a protein and small molecule, we found preferred amino acid residues at the interaction sites. These preferences can be the basis for predicting protein function from genomic sequence and protein 3D structures. The data pertaining to these small molecules were collected in a database named Het-PDB Navi., which is freely available at http:// daisy.nagahama-i-bio.ac.jp/golab/hetpdbnavi.html and linked to the official PDB home page.

    DOI PubMed

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    38
    Citation
    (Scopus)
  • Structure and function of a family 10 β-xylanase chimera of Streptomyces olivaceoviridis E-86 FXYN and Cellulomonas fimi cex

    Kaneko, S., Ichinose, H., Fujimoto, Z., Kuno, A., Yura, K., Go, M., Mizuno, H., Kusakabe, I., Kobayashi, H.

    Journal of Biological Chemistry   279 ( 25 ) 26619 - 26626  2004  [Refereed]

     View Summary

    The catalytic domain of xylanases belonging to glycoside hydrolase family 10 ( GH10) can be divided into 22 modules (M1 to M22; Sato, Y., Niimura, Y., Yura, K., and Go, M. ( 1999) Gene (Amst.) 238, 93 - 101). Inspection of the crystal structure of a GH10 xylanase from Streptomyces olivaceoviridis E-86 (SoXyn10A) revealed that the catalytic domain of GH10 xylanases can be dissected into two parts, an N-terminal larger region and C-terminal smaller region, by the substrate binding cleft, corresponding to the module border between M14 and M15. It has been suggested that the topology of the substrate binding clefts of GH10 xylanases are not conserved (Charnock, S. J., Spurway, T. D., Xie, H., Beylot, M. H., Virden, R., Warren, R. A. J., Hazlewood, G. P., and Gilbert, H. J. ( 1998) J. Biol. Chem. 273, 32187 - 32199). To facilitate a greater understanding of the structure-function relationship of the substrate binding cleft of GH10 xylanases, a chimeric xylanase between SoXyn10A and Xyn10A from Cellulomonas fimi (CfXyn10A) was constructed, and the topology of the hybrid substrate binding cleft established. At the three-dimensional level, SoXyn10A and CfXyn10A appear to possess 5 subsites, with the amino acid residues comprising subsites -3 to +1 being well conserved, although the +2 subsites are quite different. Biochemical analyses of the chimeric enzyme along with SoXyn10A and CfXyn10A indicated that differences in the structure of subsite +2 influence bond cleavage frequencies and the catalytic efficiency of xylooligosaccharide hydrolysis. The hybrid enzyme constructed in this study displays fascinating biochemistry, with an interesting combination of properties from the parent enzymes, resulting in a low production of xylose.

    DOI PubMed

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    24
    Citation
    (Scopus)
  • 3P285 Search for DNA repair related genes in Deinococcus radiodurans genome

    Yura K., Kono H., Go N.

    Seibutsu Butsuri   44   S261  2004

    DOI CiNii

  • 3P286 Computational analyses of eRF1 molecular surface that is important for stop codon interactions

    Kim Oanh, Yura K., Go N., Harumoto T.

    Seibutsu Butsuri   44   S261  2004

    DOI CiNii

  • 2SD01 PDB alert system for finding the latest New Fold

    Koike R., Kinoshita K., Yura K., Ota M.

    Seibutsu Butsuri   44   S17  2004

    DOI CiNii

  • Erratum: Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates (Journal of Eukaryotic Microbiology 51:2 (227-233))

    Kim, T.P., Yura, K., Go, N., Harumoto, T.

    Journal of Eukaryotic Microbiology   51 ( 3 ) 338 - 338  2004

    DOI

    Scopus

  • Erratum: Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates (Journal of Eukaryotic Microbiology (2004) 51:2 (227-233))

    Kim, O.T.P., Yura, K., Go, N., Harumoto, T.

    Journal of Eukaryotic Microbiology   51 ( 4 ) 495 - 495  2004

  • Integrative annotation of 21,037 human genes validated by full-length cDNA clones

    Imanishi, T., Itoh, T., Suzuki, Y., O'Donovan, C., Fukuchi, S., Koyanagi, K.O., Barrero, R.A., Tamura, T., Yamaguchi-Kabata, Y., Tanino, M., Yura, K., Miyazaki, S., Ikeo, K., Homma, K., Kasprzyk, A., Nishikawa, T., Hirakawa, M., Thierry-Mieg, J., Thierry-Mieg, D., Ashurst, J., Jia, L., Nakao, M., Thomas, M.A., Mulder, N., Karavidopoulou, Y., Jin, L., Kim, S., Yasuda, T., Lenhard, B., Eveno, E., Suzuki, Y., Yamasaki, C., Takeda, J.-I., Gough, C., Hilton, P., Fujii, Y., Sakai, H., Tanaka, S., Amid, C., Bellgard, M., de Fatima Bonaldo, M., Bono, H., Bromberg, S.K., Brookes, A.J., Bruford, E., Carninci, P., Chelala, C., Couillault, C., de Souza, S.J., Debily, M.-A., Devignes, M.-D., Dubchak, I., Endo, T., Estreicher, A., Eyras, E., Fukami-Kobayashi, K., Gopinath, G.R., Graudens, E., Hahn, Y., Han, M., Han, Z.-G., Hanada, K., Hanaoka, H., Harada, E., Hashimoto, K., Hinz, U., Hirai, M., Hishiki, T., Hopkinson, I., Imbeaud, S., Inoko, H., Kanapin, A., Kaneko, Y., Kasukawa, T., Kelso, J., Kersey, P., Kikuno, R., Kimura, K., Korn, B., Kuryshev, V., Makalowska, I., Makino, T., Mano, S., Mariage-Samson, R., Mashima, J., Matsuda, H., Mewes, H.-W., Minoshima, S., Nagai, K., Nagasaki, H., Nagata, N., Nigam, R., Ogasawara, O., Ohara, O., Ohtsubo, M., Okada, N., Okido, T., Oota, S., Ota, M., Ota, T., Otsuki, T., Piatier-Tonneau, D., Poustka, A., Ren, S.-X., Saitou, N., Sakai, K., Sakamoto, S., Sakate, R., Schupp, I., Servant, F., Sherry, S., Shiba, R., Shimizu, N., Shimoyama, M., Simpson, A.J., Soares, B., Steward, C., Suwa, M., Suzuki, M., Takahashi, A., Tamiya, G., Tanaka, H., Taylor, T., Terwilliger, J.D., Unneberg, P., Veeramachaneni, V., Watanabe, S., Wilming, L., Yasuda, N., Hyang-Yoo, S., Stodolsky, M., Makalowski, W., Go, M., Nakai, K., Takagi, T., Kanehisa, M., Sakaki, Y., Quackenbush, J., Okazaki, Y., Hayashizaki, Y., Hide, W., Chakraborty, R., Nishikawa, K., Sugawara, H., Tateno, Y., Chen, Z., Oishi, M., Tonellato, P., Apweiler, R., Okubo, K., Wagner, L., Wiemann, S., Strausberg, R.L., Isogai, T., Auffray, C., Nomura, N., Gojobori, T., Sugano, S.

    PLoS Biology   2 ( 6 ) e162  2004  [Refereed]

     View Summary

    The human genome sequence defines our inherent biological potential
    the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB
    http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

    DOI PubMed

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  • Genome function prediction based on transcription systems

    Kono H., Yura K., Go N.

    Seibutsu Butsuri   43   S3  2003

    DOI CiNii

  • 3D-keynote: genome function prediction based on protein module

    Yura, K., Go, M.

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme   47 ( 8 Suppl ) 1090 - 1096  2002  [Refereed]

    PubMed

  • Module shuffling of a family F/10 xylanase: Replacement of modules M4 and M5 of the FXYN of Streptomyces olivaceoviridis E-86 with those of the Cex of Cellulomonas fimi

    Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.

    Protein Engineering   13 ( 12 ) 873 - 879  2000

     View Summary

    To facilitate an understanding of structure-function relationships, chimeric xylanases were constructed by module shuffling between the catalytic domains of the FXYN from Streptomyces olivaceoviridis E-86 and the Cex from Cellulomonas fimi. In the family F/10 xylanases, the modules M4 and M5 relate to substrate binding so that modules M4 and M5 of the FXYN were replaced with those of the Cex and the chimeric enzymes denoted FCF-C4, FCF-C5 and FCF-C4,5 were constructed. The kcat value of FCF-C5 for p-nitrophenyl-β-D-cellobioside was similar to that of the FXYN (2.2 s-1)
    however, the kcat value of FCF-C4 for p-nitrophenyl-β-D-cellobioside was significantly higher (7.0 s-1). The loss of the hydrogen bond between E46 and S22 or the presence of the I49W mutation would be expected to change the position of Q88, which plays a pivotal role in discriminating between glucose and xylose, resulting in the increased kcat value observed for FCF-C4 acting on p-nitrophenyl-β-D-cellobioside since module M4 directly interacts with Q88. To investigate the synergistic effects of the different modules, module M10 of the FCF-C4 chimera was replaced with that of the Cex. The effects of replacement of module M4 and M10 were almost additive with regard to the Km and kcat values.

    PubMed

  • Protein folding and genome evolution

    M Go, K Yura

    OLD AND NEW VIEWS OF PROTEIN FOLDING   1194   239 - 248  1999  [Refereed]

     View Summary

    Eukaryotic genes encoding proteins are split by introns. Introns do not have information of protein amino acid sequences and they are spliced out during maturation of mRNA. Only exons are translated into proteins. Exon shuffling mediated by introns has been hypothesized as a molecular mechanism to shuffle protein segments, creating new functional proteins during evolution. We have shown that intron positions are correlated with module boundaries. A module is a small compact structural unit of a globular protein. As expected from the module-intron correlation, shuffling of a phosphate-binding module among DNA manipulating proteins was observed. Based on a compact conformation of a module, we expected mechanical stability of a single module. Molecular dynamics studies indeed show that a single module of barnase has mechanical stability. Such stability of a single module, together with the correlation between module boundaries and intron positions, implies that modules were combined into globular domains through exon shuffling during genome evolution. To investigate a role of module in protein folding, we designed a mini-protein by deleting one module from barnase and we could show conformational stability of the mini-barnase. The module engineering in barnase implies an independent behavior of the local region corresponding to a module on protein conformation. Hypothetical role of modules in folding process is also discussed.

  • An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivaceoviridis E-86 by module shuffling with the Cex of Cellulomonas fimi and by site-directed mutagenesis

    Kaneko, S., Kuno, A., Fujimoto, Z., Shimizu, D., MacHida, S., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Kusakabe, I., Hayashi, K.

    FEBS Letters   460 ( 1 ) 61 - 66  1999  [Refereed]

     View Summary

    Although the amino acid homology in the catalytic domain of FXYN xylanase from Streptomyces olivaceoviridis E-86 and Cex xylanase from Cellulomonas fimi is only 50%, an active chimeric enzyme was obtained by replacing module 10 in FXYN with module 10 from Cex, In the family F/10 xylanases, module 10 is an important region as it includes an acid/base catalyst and a substrate binding residue. In FXYN, module 10 consists of 15 amino acid residues, while in Cex it consists of 14 amino acid residues. The K-m and k(cat) values of the chimeric xylanase FCF-C10 for PKP-xylobioside (PNP-X-2) were 10-fold less than those for FXYN, CD spectral data indicated that the structure of the chimeric enzyme was similar to that of FXYN, Based on the comparison of the amino acid sequences of FXYN and Cex in module 10, we constructed four mutants of FXYN, When D133 or S135 of FXYN,vas deleted, the kinetic properties were not changed from those of FXYN. By deletion of both D133 and S135, the K-m value for PNP-X-2 decreased from the 2.0 mM of FXYN to 0.6 mM and the k(cat) value decreased from the 20 s(-1) of FXYN to 8.7 s(-1). Insertion of Q140 into the doubly deleted mutant further reduced the K-m value to 0.3 mM and the k(cat) value to 3.8 s(-1). These values are close to those for the chimeric enzyme FCF-C10, These results indicate that module 10 itself is able to accommodate changes in the sequence position of amino acids which are critical for enzyme function, Since changes of the spatial position of these amino acids would be expected to result in enzyme inactivation, module 10 must have some flexibility in its tertiary structure. The structure of module 10 itself also affects the substrate specificity of the enzyme. (C) 1999 Federation of European Biochemical Societies.

    DOI

    Scopus

    28
    Citation
    (Scopus)
  • Module structure and function of glutamyl-tRNA synthetase

    M Tateno, M Mizutani, K Yura, O Nureki, S Yokoyama, M Go

    TRACING BIOLOGICAL EVOLUTION IN PROTEIN AND GENE STRUCTURES     53 - 63  1995  [Refereed]

  • Helix-turn-helix module distribution and module shuffling

    K Yura, M Go

    TRACING BIOLOGICAL EVOLUTION IN PROTEIN AND GENE STRUCTURES     187 - 195  1995  [Refereed]

  • Erratum: Structure of the human CCG1 gene: Relationship between the exons/introns and functional domain/modules of the protein (Gene, 141 (1994) 193-200))

    Nakashima, T., Sekiguchi, T., Sunamoto, H., Yura, K., Tomoda, S., Go, M., Kere, J., Schlessinger, D., Nishimoto, T.

    Gene   148 ( 2 ) 375 - 375  1994  [Refereed]

    DOI

    Scopus

  • Repeat of a helix–turn–helix module in DNA-binding proteins

    Go, M., Yura, K., Tomoda, S.

    Protein Engineering, Design and Selection   6 ( 6 ) 621 - 628  1993  [Refereed]

     View Summary

    Helix–turn–helix motif is one of the common motifs observed in DNA-binding proteins. The motif interacts with DNA double helix and recognizes specific base sequences. It is assumed that the helix–turn–helix motif appears only once in seven prokaryotic transcriptional repressors of which 3-D structures have been determined by X-ray crystallographk studies. These prokaryotic repressors consist of several a-helices connected with turns. We report here that these repressors are decomposable into helix–turn–helix modules and their connectors. A module is defined as a compact structural unit with consecutive amino acid residues in a globular protein. Each of the helix- turn -helix motifs in the seven proteins corresponds approximately to a single helix-turn—helix module consisting of approximately 13 amino acids. Identification of modules of seven prokaryotic repressors and comparisons of then tertiary structures led to the conclusion that three of these DNA-binding proteins contain more than one helix–turn–helix module with a structure similar to the helix-turn-heUx motif. The difference in module organization of these DNA-binding proteins paves the way for further classification of the DNA-binding proteins with the helix- turn -helix motif. The structural repertoire of these transcriptional regulators was increased through different utilizations in the number of helix–turn–helix and other modules. The difference in DNA base recognition ability in these helix–turn–helix modules is ascribed to a difference in size of a side chain at the fifth residue from Gly, on the turn. © 1993, Oxford University Press.

    DOI PubMed

    Scopus

    11
    Citation
    (Scopus)

▼display all

Books and Other Publications

  • 実験医学別冊 創薬研究のための相互作用解析パーフェクト

    由良 敬, 鈴木 博文, 栗栖 源嗣, 川端 猛, 木下 賢吾, 白井 剛, 土方 敦司, 田之倉 優( Part: Joint author)

    YODOSHA  2021.12

  • ニューバイオフィジックス 2 遺伝子の構造生物学(共著)

    共立出版  1998

  • Helix-turn-helix module distribution and module shuffling.(共著)

    Tracing Biological Evolution in Protein and Gene Structures  1995

  • Module Structure and Function of Glutamyl-tRNA Synthetase.(共著)

    Tracing Biological Evolution in Protein and Gene Structures  1995

  • Some remark on protein folding(共著)

    Protein Structural Analysis, Folding and Design  1990

Research Projects

  • Elucidation of the egg diapause mechanism of the Teleogryllus emma based on comparative transcriptome analysis

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2021.04
    -
    2024.03
     

  • Building Inventory of Evolution and Luminescent Mechanisms of Bioluminescent Proteins

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2019.04
    -
    2024.03
     

  • A novel functional antigen receptor TMD module identified as an SLE-associating SNP-related structure

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2018.04
    -
    2023.03
     

  • Quantitative evaluation of disinfection mechanism using techniques of cell biology and computational biology

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2017.04
    -
    2020.03
     

    Otaki Masahiro

     View Summary

    In chlorine or ozone treatment, E.coli with fluorescent protein in cells was prepared by genetic engineering, and it became possible to quantitatively evaluate cell membrane damage from the leakage amount of fluorescent protein after treatment. Up to three types of E.coli with fluorescent protein were made possible, and by changing the protein expression site, it was possible to evaluate the damage by distinguishing between the extracellular membrane and the inner membrane. By chlorination of these E. coli, the difference in the mechanism of action of HOCl and OCl ion on the cell membrane could be clarified. It was also clarified that the cytosol, not the cell membrane, is the main action site for both ozone-dissolved water and ozone aeration.
    In UV treatment, it was clarified that different forms of nucleic acid (RNA, DNA, single-stranded, double-stranded) and different amounts of thymine affect the UV tolerance.

  • The roles of the G-quadruplex-binding activity of human ORC in replication origin establishment

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2015.04
    -
    2018.03
     

    Waga Shou, KATAHIRA Masato, YURA Kei

     View Summary

    Human ORC, one of the replication initiation proteins, exhibits preferential binding to G-quadruplex (G4)-formable single-stranded DNA (ssDNA) or RNA. To elucidate the biological roles of this activity, we analyzed the function of the human ORC1 subunit, which is known to possess the activity. We have found that the mutated ORC1, in which G4-motif ssDNA binding activity is reduced, exhibits abnormal localization in human cell nuclei and also that the N-terminal region, in which G4-motif ssDNA binding domains exist, has DNA supercoiling activity. These suggest that G4-motif ssDNA binding activity may be required for proper chromatin binding of ORC and involved in some structural changes of origin DNA during replication initiation.

  • Comprehensive prediction of RNA-protein interactinos

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2013.04
    -
    2016.03
     

    Asai Kiyoshi, YURA Kei

     View Summary

    The aim of the research was to predict the RNA-protein interactions for non-coding RNAs and function-known proteins. Our analysis of RNA-protein complex in PDB showed that the nucleotides that do not form base-pairs in RNA 2D structures but form hydrogen bond with amino acids have lower base-pairing probabilities than the nucleotides that form neither base-pairs or hydrogen bonds with amino acids. We developed a new method to understand the landscape of the distribution of RNA 2D structures, by efficiently calculating the probabilities of all the structures with specific Hamming distances from the canonical structures. In order to predict the joint structure of RNA-protein complex, we performed rigid body docking simulations. After revising the force field for RNAs, our docking simulations showed better accuracy than previous methods, and we reported that in a peer reviewed journal.

  • Identification of novel DOPA ligands and electrophysiological analysis of DOPA-induced response

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2008
    -
    2010
     

    GOSHIMA Yoshio, TAKAHASHI Takuya, YAGAMI Tatsuro, KAJIWARA Yasuhiro, YURA Kei

     View Summary

    DOPA is a novel neurotransmitter candidate in the central nervous system. In an attempt to identify a specific receptor(s) for DOPA, we have searched for selective and stable DOPA ligands. We found a positive fraction in L-threo-dihydroxyphenyserine-containing solution to induce depressor and bradycardic response when microinjected into the nucleus tractus solitarii (NTS) of anesthetized rats. In multiple electrode array system, we also found biphasic response to DOPA in NTS area of rat brain stem slices. While conducting this project, we newly identified a receptor candidate for DOPA.

  • Elucidation of the binding mode of DNA repair promoting protein to strand breaks

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2007
    -
    2009
     

    NARUMI Issay, KUROKI Ryota, YURA Kei

     View Summary

    Crystal structure analysis of the Deinococcus radiodurans DNA repair promoting protein PprA was carried out at 1.35 A resolution, and the spatial configuration of amino acids important for DNA binding was elucidated. PprM protein that modulates pprA expression was identified. A novel plasmid vector was developed for Deinococcus.

  • Studying Function of Alternative Splicing Products Based on Protein Structure Modeling

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2006
    -
    2009
     

    GO Mitiko, SHIONYU Masafumi, YURA Kei

     View Summary

    The number of genes in the genome was turned out to be unexpectedly small and alternative splicing (AS), a mechanism to produce more than one product out of a single gene, is expected to fill the gap in the numbers. It is difficult to experimentally elucidate the mechanisms of functional diversity of proteins produced by alternative splicing of the single genes. We built methods to identify AS products from the measured data, to predict structures of AS products (proteins), and to estimate difference of biochemical function of the products. The methods elucidated the differences in a number of cases.

  • Development of a method to obtain information for prediction of interacting structres of biomolecules

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2007
    -
    2008
     

    YURA Kei

  • 低分解能生体分子像からの原子構造構築技法

    JST戦略的創造研究推進制度(研究チーム型) (戦略的基礎研究推進事業:CREST)

    Project Year :

    2005
    -
    2007
     

     View Summary

    電子顕微鏡による一分子測定像から原子座標構造を構築する技術開発とその実データへの適用。超分子を構成するサブユニットの立体構造は、X線結晶解析により単独で決定されている場合が多くなっているので、それらの原子座標を適確に電子顕微鏡像にあてはめる方法の開発研究。具体的には、サブユニットのホモロジーモデリング、サブユニット間界面の予測、3次元像のあてはめ、あてはめ構造の最適化などバイオインフォマティクスや分子動力学シミュレーション研究とその適用。

  • Function annotation of DNA repair related proteins using molecular evolution information and computer simulation of protein dynamics

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2004
    -
    2006
     

    YURA Kei, ISHIDA Hisashi, HIGUCHI Mariko

     View Summary

    One of the hurdles that the field of genome biology is facing is to elucidate function of proteins deduced from genome nucleotide sequences. The best way to determine function of proteins is to carry out in vivo/in vitro experiments, yet the huge number of predicted proteins precludes performing whole types of experiments to each protein. Computational prediction of protein function can limit the necessary experiments to perform and can accelerate experimental function annotation. In this research, we have launched a project to identify functionally import amino acid residues in protein by computer simulation of protein dynamics and integrate the obtained data to the data of amino acid conservation gained by multiple sequence alignment of homologous proteins. Integration of both pieces of information was expected to improve the functional annotation of proteins. In this project we have succeeded in building database for DNA repair related proteins, improvement of functional annotation of MutT homologs (especially the ones derived from Deinococcus radiodurans), improvement of functional annotation of RuvA homologs, and improvement of functional annotation of DNA photolyase homologs. Especially in the case of DNA photolyase homologs, the correlation between the existence of functionally important residues identified by protein dynamics simulations and the conservation of amino acid residues was clearly observed. Protein dynamics simulations identified one amino acid residue crucial in an electron transfer pathway from FAD to damaged DNA. In the DNA photolyase homologs, the residues were almost completely conserved in proteins experimentally identified as DNA repair proteins, not completely mutated in proteins experimentally identified as non-DNA repair proteins. The residue was found to be a good maker for identifying DNA repair functions in DNA photolyase family (manuscript submitted).

  • タンパク質の多様性獲得戦略の解明に基づいたゲノム情報の解読

    日本学術振興会  科学研究費助成事業

    Project Year :

    2004
     
     
     

    郷 通子, 高橋 健一, 加藤 晃一, 鈴木 利治, 古川 清, 由良 敬

     View Summary

    生物がゲノムに内包された限られた数の遺伝子を駆使して天文学的ともいえるタンパク質の多様性を獲得している戦略の全体像を俯瞰的に捉えることは、ゲノム情報を読み解くうえで極めて重要である。そこで、以下のような企画調査を行い、タンパク質多様性獲得戦略に関するこれまでの研究と今後の展開に対する指針を検討した。
    2回の班会議の開催(7月16-17日、長浜;12月4日、東京)、3回の公開シンポジウムの開催(第27回日本分子生物学会年会ワークショップW3E「タンパク質の多様性獲得戦略」、12月10日、神戸;「選択的スプライシングによる多様性の創造」、12月4日、東京;「Strategies for the acquirement of functional diversity of proteins(タンパク質の多様性は限られたゲノム情報からいかにして生み出されるか?)」、1月20日、東京)、5名の海外研究者の招聘(Adrian R.Krainer(Cold Spring Harbor Laboratory)、E.Yvonne Jones(University of Oxford)、Claudio Joazeiro(Genomics Institute of the Novartis Research Foundation)、Michiko N.Fukuda(The Burnham Institute)、Jianxin Bao(Washington University))。
    これらの活動を通して得た指針に基づき、タンパク質多様性獲得戦略の全体像把握に向けた研究を推進していくために、科学研究費補助金「特定領域研究」の平成17年度新規発足申請(申請領域名「タンパク質機能の多様性獲得戦略」)を行った。

  • 遺伝子同時転写単位同定にもとづく新規DNA修復関連タンパク質の予測

    日本学術振興会  科学研究費助成事業

    Project Year :

    2004
     
     
     

    由良 敬

     View Summary

    本研究では、放射線抵抗性細菌であるDeinococcus radioduransをモデル生物として、機能未知遺伝子がコードするタンパク質の中から新規のDNA修復関連タンパク質を予測し実証実験によって予測を確かめることを試みた。D. zadioduransの全ゲノム配列を取得し、Open Reading Frame (ORF) をアサインした。ORF間スペーサー領域の塩基数を測定して、既知のオペロンにおけるスペーサー領域の塩基数をもとに、新規オペロンの推定をおこなうことができた。推定オペロンと開発継続中のDNA修復関連タンパク質のデータベースを組み合わせることで、D. radioduransのゲノムからDNA修復関連タンパク質とともにオペロンを形成する機能未知遺伝子を見いだした。これら遺伝子はDNA修復関連タンパク質と同時に転写される可能性がある。これら遺伝子のうち、約60%が新規のDNA修復関連タンパク質であろうことを理論的にみつもることができた。新規DNA修復関連タンパク質と推定された遺伝子の中から数個を選び、日本原子力研究所高崎研究所において実証実験をおこなった。その結果、これらの機能未知タンパク質をコードする遺伝子のうち、2っはDNA修復関連タンパク質をコードしていることが実証できた。ひとつはDNA架橋剤による損傷修復に関与する亜鉛フィンガーをもつD. zadioduTansとその近縁種にのみみられる遺伝子であり (Kiuchi et al., J. Bacteriol. 投稿中)、もう一つはγ線損傷の修復に関連するアセチル転移酵素と推定された (Yura, Narumi, et al., Mol. Microbio1. 投稿準備中)。

  • Decoding of genome function and evolution based on the 3D structures of proteins

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    2000
    -
    2004
     

    GO Mitiko, TAKAHASHI Kenichi, SHIRAI Tsuyoshi, SODA Kunitsugu, YURA Kei

     View Summary

    As a functional prediction method for ORFs inferred in genome sequences, we developed a method to convert structural and functional properties of protein modules into amino acid sequence patterns, called "3D-keynote". Using the method, we inferred a function of ORF, slr0197 from a cyanobacterium genome, which was subsequently verified by collaborative experiments. Furthermore, we made an automatic system to generate 3D-keynotes for each kind of functions and accomplished generations of 196 kinds of 3D-keynotes, whose prediction accuracies were evaluated to be about 85% on an average. Applying these to a cyanobacterium genome, we obtained clues for inferring the functions for about 12% of function-unknown ORFs. The 3D-keynotes were also used for human genome annotation in H-invitational (Yura & Go).
    A sugar-protein interaction prediction system was developed. Strict and loose evaluations of the prediction accuracy resulted in 25 and 66%, respectively, which were better than other existing methods. To experimentally verify the prediction system, crystal structure analyses of sugar-binding proteins such as lectin, were done. We determined structures of six novel complex forms of congerin and obtained evidences supporting the existence of sugar-binding sites predicted by the prediction system (Shirai).
    A chain topology of hydrophobic cluster residues was found to be a reduced representation of a whole chain of the protein molecule. From molecular dynamics simulations of a pseudo-peptide chain composed of hydrophobic cluster residues and cluster analyses of the generated structures, we defined roles of hydrophobic cluster residues as their non-specific hydrophobic aggregation forces made the protein chain compact to decrease the search space for conformations and accelerate the folding process (Soda).
    Exhaustively analyzing human full-length cDNA data by the method we developed to identify alternative splicing (AS) regions, we found that most regions altered by AS were shorter than common sizes of protein domains, and indicated possibilities that AS of transcripts may lead to structural destabilization of and/or loss of interaction sites on their protein products and result in changing pathways of the protein network involved (Go & Takahashi).

  • 進化情報を用いたDNA修復酵素複合体の相互作用部位予測

    日本学術振興会  科学研究費助成事業

    Project Year :

    2003
     
     
     

    由良 敬

     View Summary

    ゲノムは放射線や化学物質による攻撃を受け続けている。これらの攻撃の結果、ゲノム配列に変化が生じるが、生物にはこの障害を修復する機構がある。また、DNA複製の際にも複製ミスは起こっているが、そのミスもほとんどの場合は修正されている。DNAの塩基配列をある程度保存することができなければ、ゲノムにコードされている情報が変化してしまい、その生物は死にいたる。ゲノムを修復するDNA修復酵素は複合体を形成していることが、生化学的な解析および立体構造解析でわかってきた。ところが、各修復システムの全立体構造が判明しているのはまれで、単体の構造もしくはドメインの構造のみが判明している場合が多い。そこでDNA修復酵素において、立体構造が判明している各サブユニットまたはドメインのどの部分が複合体形成に関与するかを、進化的情報から抽出する方法の開発と適用を目的として本研究を開始した。本研究の結果以下の3点を達成した。
    1)DNA修復関連タンパク質のアミノ酸配列、ゲノム上の位置、及び相互作用の情報を収集したデータベースを継続的に発展させた。その結果、現在133種類のDNA修復関連タンパク質が知られており、そのうちの82種類については、少なくともドメインの立体構造がホモロジーモデリングによって構築可能であることがわかった。
    2)タンパク質立体構造のデータベースを用いて、20種のアミノ酸残基がタンパク質の内部に埋まる傾向を調べたところ、従来の疎水性指標とは異なる傾向にあることがわかった。
    3)上記2つのデータを用いてDNA修復関連タンパク質の相互作用面を調べたところ、RuvAの他タンパク質(RuvB)との相互作用面を正しく推定することができた。また塩基除去修復酵素AAGには、他の修復関連タンパク質と相互作用しそうな表面が存在しないことが推定され、AAGが単体で損傷DNAに作用することが推定された。

  • DNA損傷修復関連タンパク質の構造と機能

    補助金

    Project Year :

    2002
    -
     
     

     View Summary

    ゲノム塩基配列から新規DNA修復関連タンパク質を見いだす計算生物学と実験の共同研究

  • 全ゲノム配列比較にもとづくDNA修復酵素の比較と分類

    日本学術振興会  科学研究費助成事業

    Project Year :

    2002
     
     
     

    由良 敬

     View Summary

    ゲノムは放射線や化学物質による攻撃を受け続けている。これらの攻撃の結果、ゲノム配列に変化が生じるが、生物にはこの障害を修復する機構がある。また、DNA複製の際にも複製ミスは起こっているが、そのミスもほとんどの場合は修正されている。DNAの塩基配列をある程度保存することができなければ、ゲノムにコードされている情報が変化してしまい、その生物は死にいたる。しかし、完全に修復してしまっては、生物は進化しない。DNA損傷の修復は、DNA修復酵素と呼ばれる一群のタンパク質によって行われていることが解明されている。放射線照射による細胞のガン化は、DNA修復酵素による修復が正常に機能しない、または間に合わないことが原因の一端となっている。このように基本的な酵素であるDNA修復用タンパク質は、DNAポリメラーゼやRNAポリメラーゼのように、すべての生物に共通に存在するのだろうか。あるいは、生物ごとに異なる種類のDNA修復酵素が存在するのであろうか。生物は進化の過程で何種類の修復酵素を生み出してきたのであろうか。以上のことを明らかにすることを目的に、研究を開始した結果以下の2点を達成した。
    1)DNA修復酵素および修復に関連するタンパク質のアミノ酸配列、ゲノム上の位置、及び相互作用の情報を収集することができ、それらを統合したデータベースを構築することができた。平成15年3月現在、試験的な公開を開始し、詳細部分の調整を行っている。
    2)データベース構築にあたり、全ゲノムが判明している生物種において、各種の修復関連タンパク質の存在の有無を調べたところ、多くの修復関連タンパク質が、保存されていないことが判明した。たとえば、ミスマッチ修復システムであるMutS, MutL, MutMは3つのタンパク質がそろって、初めて機能するはずであるが、生物によっては、3つが完全にそろっていない、または1つが重複している場合があることがわかった。

  • モジュール3Dキーノートを用いたゲノム機能予測法の開発

    日本学術振興会  科学研究費助成事業

    Project Year :

    2001
    -
    2002
     

    由良 敬

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    全ゲノム配列が発表されている生物種は、100種を越えた。生体で機能している高分子は大部分がタンパク質であるため、集積されたゲノム配列にどのような機能を持ったタンパク質があるかを知る必要がある。しかし、ゲノム配列からタンパク質の機能を推定する方法はまだ確立していない。ゲノムにあるORFの約半数は機能が推定できていない。申請者は立体構造が類似であり、機能部位の詳細な構造が類似のリン酸基結合モジュールを、まったく異なる転写因子およびDNA重合修復酵素に見いだしてきた(K.Yura, et al. 1999a)。これらのモジュールのアミノ酸配列には明らかな類似性はないが、立体構造および機能部位が類似していることより、何らかの類似性が配列にあることが期待され、立体構造形成および機能に重要な残基に注目することで、アミノ酸配列のパターンを見いだし3Dキーノートと命名した(Yura, et al. 1999b)。本研究課題では、ゲノム配列中のORFから各種の3Dキーノートと一致する部位を見つける方法を確立することで、ORFの機能推定を行う手法を開発した。平成13年度までに3Dキーノートの作成方法がほぼ確立したのを受けて、平成14年度では、3Dキーノート作成方法の自動化をほぼ確立し、ゲノム配列決定が終了している全ゲノム配列に対して、約200種類の3Dキーノートを適用することができた。それらの予測結果を容易に検索できるようにするためのデータベースを構築し、研究室内において試験運用を開始することができた。また3Dキーノートによる予測結果がどの程度正しいかを実験的に検証するために、シアノバクテリアの実験家に予測結果を提示し、実証実験を開始することができた。現在までに実験結果を予測方法に還元することまでは至っていないが、実験と理論のよい組み合わせを形成することはできた。

  • Protein function and module shuffling

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1999
    -
    2002
     

    GO Mitiko, TOH Hiroyuki

     View Summary

    The aim of this research project was to develop a method to predict function of proteome on the bases of knowledge of protein module.
    Since module is defined by using three-dimensional structure of proteins, its conformation and function are conserved during evolutionary processes. Thus, it is valuable, to use module information than to use amino acid sequence signature or motifs in prediction of genome function. We have deduced sequence pattern information by classification of modules, developed 3D-key note method and applied it to predict function of genome sequences of various species. Our prediction for a gene was proved experimentally in cyanobacterium Synechocystis. Particularly, we applied our method to annotate human genome. We published several papers and data bases as products of this project (URL:http://daisy.nagahama-i-bio.ac.jp/golab/hetpdbnavi.html), (URL:http://daisy.nagahama-i-bio.ac.jp/famsbase/index.html), (URL:http://daisy.nagahama-i-bio.ac.jp/keynote/AK074299.html).

  • Development of a method to predict protein function based on module classification

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1999
    -
    2002
     

    GO Mitiko, YURA Kei, TAKAHASHI Ken-ichi

     View Summary

    The aim of this study is (1) to clarify that key components of protein functions are localized to compact short segments, modules, and (2) to elucidate principle of protein design using modules as building blocks. In consequence, we found various kinds of protein functions were assigned to modules. For example, (1) the functional sites of the catalytic domain of family 10 xylanase are localized to some of the modules; (2) in many case, ligands for certain metal ions exist within one or two modules. Furthermore, modules with similar structure and function are frequently observed in various proteins, which indicates the possibility that the modules were shuffled. In addition, (3) common modules are found to be used for protein-protein interaction; (4) only two modules are used in subunit interaction of hemoglobin, which could explain why subunit interactions of hemoglobin are diversified in various lineage. We also showed that modules can be deleted or shuffled by experiments. For example, (1) module M2 in barnase was deleted without loss of the stable three-dimensional structure similar to the native structure and the cooperative folding behavior. (2) a chimera xylanase, which was made by exchange of module M10 between two kinds of xylanases in family 10, maintained the structure and function, though the enzyme activity decrease by a tenth. This study has clarified a basic principle for module-based protein design from both views of computer science and experimental science.

  • ゲノムからの蛋白質 構造 機能予測

    科学研究費補助金

    Project Year :

    2001
    -
     
     

  • 金属イオン結合モジュールの金属配位様式の共通性・多様性

    日本学術振興会  科学研究費助成事業

    Project Year :

    1999
    -
    2000
     

    由良 敬

     View Summary

    本年度は、立体構造が判明しているタンパク質で数多く見られるすべての金属イオン、カルシウム、マグネシウム及び亜鉛イオンにおいて、それぞれのイオンがいくつのモジュールに配位するのか、及びそれぞれのイオンの配位部位に類似のモジュールが存在するのかを調べた。タンパク質における金属イオン配位子の今までの研究では、タンパク質における金属イオンの配位子は、アミノ酸配列上全体に散らばっていると考えられていた。しかし、多くのタンパク質で調べたところ、カルシウム、マグネシウム、亜鉛イオンにおいては、約75%の場合は配位子が局在していることがわかった。タンパク質のコンパクトな構造単位であるモジュールと金属イオン配位子の関係を見ると、金属イオン配位子は、ひとつないしは二つのモジュールに局在していることがわかった。これら金属イオン配位子を持つモジュールの立体構造を比較すると、どの金属イオンにおいても、類似立体構造をもつ金属イオン配位モジュールが存在することがわかった。各金属イオンを配位する類似立体構造のモジュールにおいて、それらのアミノ酸配列を比較すると、モジュール全体にわたって類似性が見られる場合と類似性が見られない場合とがある。モジュール全体にわたって類似性が見られる場合は、すでにアミノ酸配列のモチーフが報告されているが、モチーフによって推定できるタンパク質の金属配位部位は、立体構造解析によって判明している金属配位部位の約30%にすぎない。立体構造が類似でアミノ酸配列モチーフが見られない場合でも、金属イオン配位子となる残基は同一または類似残基であった。特に亜鉛イオンの場合はヒスチジンかシステインによって配位されている場合が約75%であった。ゲノム配列から予測される機能未知アミノ酸配列が大量にデータベースに存在することより、類似立体構造を持つ金属イオン配位モジュールのアミノ酸配列から何らかの共通性を見いだし、アミノ酸配列から金属配位モジュールを推定できるようにすることが次の課題となる。

  • Protein structure, comparison, prediction, and design

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1995
    -
    1999
     

    GO Nobuhiro, YURA Kei, NISHIKAWA Ken, WAKO Hiroshi, YOMO Tetsuya, ISHIMORI Koichiro

     View Summary

    Natural history group (Go, Yura, Wako, Nishikawa, Mitaku, and Umeyama)
    From a classification of the spatial arrangements of the secondary structure elements, Go discovered 'the symmetry rule', whish states that apair of similar protein folds, having no common ancestor, tend to possessan internal symmetry in their fold. Yura found two types of 'modules', a phosphate binding module observed commonly in polymerases and transcription factors, and a substrate-specificity determining module of peroxidases. A newly developed method for detecting similarity in the atomic level revealed a lot of similar ATP binding structures in totally different folds (Go). Wako developed an efficient algorithm of expressing the local environment by a code representation. A new secondary structure prediction method was developed by Nishikawa, who applied the threading method for this purpose. As for the structural prediction for membrane bound proteins, Mitaku improved his method to predict the structure of bacteriorhodopsin correctly. Umeyama established a fully automated algorithm of homology modeling, which is estimated to give a sufficient accuracy.
    Design group (Yomo and Ishimori)
    Yomo found in random mutagenesis experiments on catalase that the thermal stability and activity of the protein is extremely robust against mutations, and that a possibility of the functional optimization by the evolutional engineering technique can enormously enhanced by the elongation of the chain length. The concept of 'module' was applied to produce chimera hemoglobin, which was synthesized by exchanging its modules each other. From such chimera proteins, Ishimori confirmed that the structural unit, module, works not only as the unit of maintaining the protein stability, but also as a unit for realizing the function of hemoglobin.

  • リン酸基結合モジュールにもとづくDNA結合部位の推定

    日本学術振興会  科学研究費助成事業

    Project Year :

    1997
    -
    1998
     

    由良 敬

     View Summary

    転写因子において塩基認識部位には共通の立体構造が存在することが知られている。それでは、これらのタンパク質のリン酸基結合部位には共通の構造が存在するのであろうか。タンパク質-DNA複合体のモジュール構造を調べたところ、DNAのリン酸基にのみ結合するモジュールが存在することがわかった。リン酸基結合モジュールを比較した結果、原核生物と真核生物の転写因子及びポリメラーゼの4つのタンパク質に、類似の立体構造・リン酸基結合様式をもつモジュールが見いだされた。これらのモジュールは塩基を認識するヘリックス・ターン・ヘリックス(HTH)モジュールと類似の立体構造をとっているが、塩基と水素結合することはなく、C末端側ヘリックスのN末端に位置する主鎖のアミノ基でDNAのリン酸基と水素結合することがわかった。これらのモジュールには、立体構造構造形成のため及び機能を実現するために固有のアミノ酸配列パターンが存在することがわかった。そのパターンを用いて全ゲノム配列が決定されたシアノバクテリアSynechocystis sp.PCC6803を検索した結果、機能未知のORF slr0197にそのリン酸基結合HTHモジュール候補が2箇所見つかった。ORF slr0197にはエンドヌクレアーゼドメインがあることが同時に予測された。このシアノバクテリアは、外来DNAをそれ自身の遺伝子に取り込むことで形質転換を起こすことが知られているが、その分子的機構は判明していない。形質転換の最初の段階は外来DNAの配列非特異的な取り込みである。他のいくつかの知見から、ORF slr0197は形質転換における外来DNA取り込みに関与していることが示唆され、DNA結合部位は2つのリン酸基HTHモジュールであることが予測された。

  • タンパク質モジュールとエクソンとの対応の普遍性

    日本学術振興会  科学研究費助成事業

    Project Year :

    1996
    -
    1998
     

    郷 通子, 由良 敬, 野口 俊之

     View Summary

    立体構造既知の蛋白質のすべてをモジュールに分解し、モジュール境界と遺伝子上のイントロンの位置との対応を統計的に調べ、モジュール境界とイントロンの対応がタンパク質に普遍的に成り立つ事実であることを明らかにすることが本研究の目的であった。
    本研究で完成したモジュール全自動同定法を使って、立体構造が既知であって原子座標が公開されているすべてのタンパク質をモジュールに分類した。最終的に50を越える多数のタンパク質について、モジュール境界とイントロンの位置が統計的に有意に相関していることを示すことができた。この結果は、モジュールとエクソンの相関がタンパク質に普遍的に成り立つ事実であることを示している。これはイントロンが生物進化において重要な役割を担ってきたことを示す、新しい構造生物学的知見である。イントロンの起源が古いことを示しており、イントロンの起源論争に大きく寄与する重要な結果が得られた。さらに、いくつかの酵素において、イントロンを介在者として、基質特異性がモジュール交換によってもたらされた可能性が示された。本研究はモジュールとエクソンの相関がタンパク質に普遍的に成り立つこと、モジュールが機能部品であることを明らかにした。特に、細胞壁の糖分解酵素であるキシラナーゼにおいては、この酵素単独でも、モジュール境界とイントロン位置が有意に相関していることがわかった。興味深いことに、基質結合部位は数個のモジュールに局在していた。イントロンはエクソンすなわちモジュールの連結や混成を仲介したデバイスであった。モジュールを部品として生物が行ったタンパク質デザインを、生物進化的束縛を離れて、人の手で行うことが可能な事を示している。これはタンパク質工学に新たな展開をもたらす結果であり、実際に、本研究の応用としてキシラナーゼのキメラタンパク質による新機能の創出に発展させることができた。

  • 転写因子のモジュール・ドメイン構成とシグナル認識

    日本学術振興会  科学研究費助成事業

    Project Year :

    1997
     
     
     

    郷 通子, 由良 敬

     View Summary

    本研究ではDNAとの複合体のX線結晶解析がなされている転写因子やDNAポリメラーゼ、修復酵素などを対象に、モジュール構成とDNAとの相互作用を解析した。その結果、機能がモジュールによって分担されていることがわかった。DNAとの相互作用は塩基特異的認識とリン酸基結合とに分けられることを、昨年度までに明らかにしている。DNPポリメラーゼや修復酵素などの触媒機能も、塩基特異的認識やリン酸基結合と同様に、数少ないモジュールに分担されていた。DNAの塩基配列を特異的に認識するモジュールとしては、ヘリックス・ターン・ヘリックス(HTH)モジュールが知られている。塩基の特異的な識別のために、共通の主鎖構造をもつモジュールHTHが使われているが、アミノ酸側鎖に個性があるから特異的な相互作用ができる。一方、DNAの主鎖骨格にはリン酸基があり、リン酸基とタンパク質との相互作用も重要である。このことはこれまであまり注目されていなかった。リン酸基結合モジュールにも、共通性のある立体構造が存在する。原核生物と真核生物由来の3種類の転写因子と真核生物由来のDNAポリメラーゼとの間に、共通のHTHモジュールが存在することを見いだした。リン酸基との相互作用の様式の詳細を調べた結果、水素結合の様式もよく似ているリン酸基結合HTHモジュールであった。これらのモジュールは、一次構造にも共通性をもつことが明らかになった。この結果から、RNAポリメラーゼαサブユニットとDNAとの相互作用部位を、相互作用の様式を含めて推定することができた。HTHモジュールは、塩基特異的認識、リン酸基結合、あるいは他のモジュールの支持台として、何回もタンパク質に組み込まれていったことが示された。

  • Development of design method to get soluble protein

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1996
    -
    1997
     

    GO Mitiko, HOJO Hironobu, YURA Kei, NOGUTI Tosiyuki

     View Summary

    In order to know structure and function of gigantic protein and protein complex, a method to cut and take out stable partial structure of protein and a method to make the partial structure soluble are needed. Our purpose is to develop a design method to take out partial structure of protein in a soluble and stable from. We intended further to verify that the designed partial structure forms soluble and stable structure in solvent. In process of molecular evolution, a fusion of domain or module occurred frequently. We showed that in reverse transcriptase, on the occasion of RNaseH domain fusion, at least 4 amino acid replacements occurred in adopting to the atomic interactions at domain contact. We applied the same method to make a partial protein structure soluble. Previously we found a barnase-like domain in RNA polymerase. We planed to cut out the barnase-like domain from RNA polymerase and designed a soluble form of isolated barnase-like domain. Then we did a chemical synthesis of the sequence. For getting soluble barnase-like domain, we established a method to replace amino acid residues using an evolutionary replacement pattern of amino acid in domain fusion. This method is applicable for the proteins whose three-dimensional structures are unknown. Also, we designed a mini-barnase by removing a module from barnasr, performed molecular dynamics and evaluated its solubility and stability by free energy calculation. Mini-barnase lacking 26 amino acid residues was chemically synthesized. We measured CD and NMR of designed mini-barnase. It was dissolved into water and took a stable structure similar to the conformation of a barnase except the excised region. Through this research, we developed a method that is useful in cutting and taking out a part of protein in soluble and stable form.

  • DNAリン酸基に結合するモジュールは共通か

    日本学術振興会  科学研究費助成事業

    Project Year :

    1996
     
     
     

    由良 敬

     View Summary

    DNAに結合するタンパク質の塩基認識部位には共通の部分構造が用いられている場合が多い。それではリン酸基と結合する部分にも、共通の構造が存在しないだろうか。本研究は、DNA結合タンパク質のリン酸基結合部位に共通のモジュールが存在するかを明らかにすることを目的に行われた。モジュールとはコンパクトな構造をもつタンパク質の構造単位である。イントロンの位置とモジュールの境界の相関より進化の単位でもあると考えられている。
    DNAとの複合体で立体構造が判明しているDNA結合タンパク質のモジュール境界を同定し、立体構造を比較した。その結果、真核生物のDNA polymerase βと原核生物の434 CroおよびArc repressorとに立体構造及びリン酸基との結合様式が共通のモジュールが見つかった。これらのタンパク質の全体構造はまったく異なる。このモジュールはN末端側とC末端側がヘリックスで構成されており、短いループでふたつのヘリックスがつながった構造をしていた。C末端側のヘリックスのN末端の主鎖の-NHがリン酸基の酸素原子と水素結合する様式が共通だった。以上のことより、DNAのリン酸基に結合する様式が共通であり、立体構造が類似のモジュールが存在することが示せた。以上のことをまとめ、論文投稿準備中である。
    それでは、塩基認識・リン酸基結合モジュールと類似部位を機能未知のタンパク質に見つけだすことで、そのタンパク質の立体構造・機能を推定することはできるだろうか?立体構造・機能が判明していないクロロプラストのIRF170タンパク質が、塩基認識・リン酸基結合モジュールをもつホメオドメインとアミノ酸配列の類似性があることがわかった。このことはIRF170がDNA結合タンパク質であることを示唆する。原核生物由来のクロロプラストにホメオドメイン様タンパク質が存在する可能性があることを初めて示した。

  • 転写因子のモジュール・ドメイン構成とシグナル認識

    日本学術振興会  科学研究費助成事業

    Project Year :

    1996
     
     
     

    郷 通子, 由良 敬

     View Summary

    本研究で明らかにしたことは、(1)転写因子のモジュール構成と機能相関、(2)プラスチドの転写産物IRF170がコードするタンパク質がホメオドメインとの類似性をもつこと、(3)逆転写酵素はRNaseHドメインと他のドメインとの融合型であるが、ドメイン融合が起きるために必要だったと推定されるアミノ酸置換の位置と数、の3点である。各項の内容は以下の通りである。(1)蛋白質のDNAへの結合は、まずリン酸基に結合し、それから塩基特異的な結合部位を探すと考えられている。塩基特異的な結合には、共通のモジュールが用いられている例が多々ある。リン酸基との結合もまた、モジュールによって担われているか?そうであるなら、リン酸基結合モジュールには共通の立体構造が存在するか?DNAとの複合体として立体構造が判明している転写因子群を対象して研究を行った結果、転写因子は塩基を特異的に認識する塩基認識モジュールと、リン酸基を非特異的に結合するリン酸基結合モジュールとの組み合わせとして構築されていることが、明らかになった。また、原核生物由来の2種類の転写因子と真核生物由来のDNAポリメラーゼとの間に、立体構造がよく似ていてリン酸基との相互作用の様式が同じリン酸基結合モジュールが見つかった。この結果はモジュールのかき混ぜの痕跡であろう。(2)はIRF170がプラスチドの分化を制御していることを示唆した。また、IRF170はらん藻にも存在することから、ホメオドメインによる遺伝子発現の制御は真核生物と原核生物の分岐以前から存在していたことが示唆された。(3)RNaseHドメインと単独ドメイン型であるRNaseHIとの構造比較を行った結果、ドメイン接触部位で最低14個の適応的なアミノ酸置換が必要であったことが示された。

  • リン酸を結合する複数のタンパク質に存在する共通のモジュール

    日本学術振興会  科学研究費助成事業

    Project Year :

    1995
     
     
     

    由良 敬

     View Summary

    全体構造は異なるがリン酸基と結合する共通の機能をもつタンパク質において、リン酸基結合部位が共通のモジュールであることを示すことを目的に本研究を行った。タンパク質立体構造のデータベースより、リン酸基と結合するタンパク質を選び出し、それらのタンパク質のモジュール境界を同定した。同定されたモジュール境界でタンパク質を分割し、モジュールの立体構造を比較した。立体構造の一致度は、二つのモジュールのCα原子を重ね合わせ、対応するCα原子の距離の自乗和の平方根(RMSD)で評価した。その結果、434croとarc repressorのふたつのタンパク質に立体構造が共通で、リン酸基と共通の様式で結合するモジュールが存在することがわかった。どちらのタンパク質もファージがもつ転写制御因子であるが、全体の立体構造は異なる。特にDNAの塩基配列を認識する構造は、434croの場合はヘリックスであるが、arc repressorの場合はストランドとまったく異なる。434croにはリン酸基と水素結合するモジュールが2つ、arc repressorには1つ存在した。434croのひとつのモジュールとarc repressorのモジュールとが両末端にヘリックスをもち、RMSD0.72Åの類似の立体構造をしていることがわかった。どちらのモジュールも、C末端側に存在するヘリックスのN末端の主鎖で、DNAのリン酸基の酸素と水素結合していることがわかった。一般にヘリックスの主鎖のアミノ基は、主鎖のカルボキシル基と水素結合している。しかしヘリックスのN末端側のアミノ基には、水素結合するカルボキシル基がない。このアミノ基がDNAのリン酸基の酸素と水素結合していた。全体構造が異なるタンパク質において、立体構造及び機能が共通のモジュールが存在したことは、これらのタンパク質が共通のリン酸結合モジュールを用いて進化してきたことを示唆する。以上のうち暫定的な結果は発表した。本論文は現在投稿準備中である。

  • 転写因子のモジュール・ドメイン構成とシグナル認識

    日本学術振興会  科学研究費助成事業

    Project Year :

    1995
     
     
     

    郷 通子, 由良 敬

     View Summary

    転写因子およびシグナル認識に関わるタンパク質の高次構造とシグナル認識機構との関連を解明するため、以下の2つを目的に本研究を行った。(1)タンパク質をモジュールに分解して、シグナル認識に関与しているモジュールを明らかにする。(2)モジュール構成とその立体構造によって機能部位を推定する。以下の実績が得られこれらの目的が達成された。
    1)転写因子TAF_<II>250(CCG1)のモジュールの機能予測:TAF_<II>250は基本転写因子TF_<II>Dの構成成分である。ヒトCCG1遺伝子は細胞周期G1期進行の調節機構に関与しているが、TAF_<II>250の遺伝子と同一であることがわかっている。郷らが独自に開発した方法により、ヒトCCG1(1,872アミノ酸残基)で予測された152個のモジュールの中で、数個のものについて、機能を推定し、さらにそのモジュールの立体構造をモデリングすることができた。DNAと結合する事が強く示唆されるモジュールが存在した。
    2)ヘリックス・ターン・ヘリックス(HTH)モジュールの機能分化:転写因子に広く存在するHTHモジュールは塩基特異的にDNAと結合するモジュールとして、従来考えられてきた。転写因子と各種のDNA結合タンパク質の立体構造を詳しく解析した結果、HTHモジュールはリン酸との相互作用を通してDNAと非特異的に相互作用するモジュールとしても、DNA結合タンパク質に広く存在していることが分かった。
    3)昆虫の変態ホルモンの高次構造の推定:カイコの脳で生産される変態ホルモンPTTHは、ヒトなどの成長因子が属するシスチンノットファミリーの一員であることが、主にジスルヒド結合のパターンと保存されたアミノ酸配列の特徴から明らかになった。

  • Classification of Protein Modules

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research

    Project Year :

    1994
    -
    1995
     

    GO Mitiko, YURA Kei, NOGUTI Tosiyuki

     View Summary

    Introns are located close to boundaries of modules, small structural units in globular proteins. This fact implies that modules are the original building blocks encoded by exons and they were fused or shuffled during molecular evolution. The purpose of this research project is to classify the modules of proteins and to indentify the common modules recruited into different proteins by fusion or shuffling.
    1.Development of classification method : We found by molecular dynamics calculation that the modules were able to be classified into groups on the basis of the similarity in their three-dimensional (3D) structures.
    2.Classification of modules : Seventy-seven proteins with sequence identity less than 40% among one another were decomposed into 950 modules. About 2/3 of them were classified into 66 groups, however, the other modules were remained without making groups together.
    3.Common modules observed in proteins : These modules had common biological functions. this result gives good evidence for exon/module shuffling among different proteins. The helix-turn-helix module seems to have diverged into three types with different roles ; the first is specific DNA sequence recognition, the second is non-specific DNA binding through the interactions with phosphates, and the third is scaffold stabilizing globular proteins.

  • シトクロムP-450camとCamリプレッサーとの共通構造

    日本学術振興会  科学研究費助成事業

    Project Year :

    1994
     
     
     

    由良 敬

     View Summary

    転写制御因子に結合する分子が、制御されている遺伝子のコードしている蛋白質の基質である場合、両蛋白質における分子結合部分に共通のモジュールが用いられていないだろうか。以上の問題に答えることを目的として、転写制御因子であるCamリプレッサー(CamR)と、制御されている蛋白質、シトクロムP-450cam(P-450cam)のアミノ酸配列をモジュール単位で比較した。CamRはDNAに結合し、カムオペロンの転写を抑制する。カンファー存在下でCamRはDNAとの親和性を弱め、その結果、カムオペロンの転写が始まる。P-450camはカムオペロンにコードされており、カンファーに酸素を転移する反応を触媒する。
    両蛋白質のアミノ酸配列比較の結果、CamRの約30残基からなる領域がP-450camの基質結合に重要とされている部位と67%の類似度を示すことがわかった。この部分は立体構造の判明しているP-450camではほぼモジュール3個分に相当した。P-450camでは、カンファーの結合様式が詳細に判明している。CamRと類似モジュールを持つ部分は基質と水素結合を形成する残基1つ、および疎水相互作用をする残基2つを含んでいた。これらのアミノ酸残基は類似の残基として保存されていた。類似の残基による保存でも問題がないことを、コンピュータ・モデリングにより確かめた。
    CamRにP-450camの基質結合モジュールが存在し、その部分で基質を結合していると推定できることより、両蛋白質が進化の過程で、共通のモジュールを共通の機能をうみだすために用いたと考えることができる。つまり、立体構造の単位であるモジュールが、カンファーを結合する機能の単位として用いられたのであろう。
    以上の結果・考察について現在投稿準備中である。

  • 転写因子のモジュール・ドメイン構成とシグナル認識

    日本学術振興会  科学研究費助成事業

    Project Year :

    1994
     
     
     

    郷 通子, 由良 敬

     View Summary

    転写因子をモジュールに分解し、シグナル認識に関与しているモジュールを明らかにし、さらにそのモジュールの立体構造によって機能部位を推定することを目的に本研究を行った。
    (1)転写因子TAF_<II>250のモジュール境界の予測:TAF_<II>250は基本転写因子TFIIDの構成成分である。九州大学の西本らにより単離されたヒトCCG1遺伝子は細胞周期G1期進行の調節機構に関与しているが、TAF_<II>250の遺伝子と同一であることがわかっている。ヒトCCGは1,872アミノ酸残基からなる大きいタンパク質である。その機能部位を調べるために、郷らが開発した方法により、モジュール構成の予測を行った。152個のモジュールからなることが予測された。
    (2)ヒトCCG1遺伝子のエキソンとCCG1のモジュール境界との対応相関:西本らによりヒトCCG1遺伝子の構造が決定され、38個のエキソンに分かれていることが明らかになった。イントロンは予測されたモジュール境界とよい相関を持つこと、モジュールは機能部位ともよく対応していることがわかった。モジュール情報をもとに、さらに詳細に機能部位を調べるための道が開けた。
    (3)Camリプレッサー(CamR)とシトクロムP-450cam(P-450cam)とに存在する共通モジュール:P-450camは立体構造が判明しており、モジュール同定ができる。基質(カンファー)を結合するモジュールがCamRにも存在することが、アミノ酸配列の類似度から推定された。CamRはカンファーをシグナルとして、カムオペロンの転写調節を行う。CamRとP-450camはカンファーという共通のシグナルを認識するモジュールを共通に取り込んだ結果、現在の機能を獲得したに違いない。

  • 蛋白質分子の構造, 機能及び進化

    その他の研究制度

    Project Year :

    1990
    -
     
     

  • Structure, function and evolution of protein

    Ordinary Research

▼display all

Misc

  • Exploration of the taurine biosynthetic pathway in the cricket superfamily

    鈴木愛菜, 伊倉貞吉, 三野流斗, 片岡孝介, 朝日透, 鈴木丈詞, 森光康次郎, 由良敬, 由良敬, 由良敬, 由良敬

    日本分子生物学会年会プログラム・要旨集(Web)   46th  2023

    J-GLOBAL

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    佐々木 元子, 川目 裕, 松尾 真理, 小杉 眞司, 櫻井 晃洋, 由良 敬, 高島 響子, 李 怡然, 松川 愛未, 大住 理沙, 神原 容子, 三宅 秀彦

    日本遺伝カウンセリング学会誌   43 ( 2 ) 144 - 144  2022.06

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    早川翔大, 片岡孝介, 阿左美優花, 由良敬, 由良敬, 鈴木丈詞, 朝日透, 朝日透

    日本応用動物昆虫学会大会講演要旨   66th  2022

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    三宅秀彦, 小杉眞司, 櫻井晃洋, 松尾真理, 川目裕, 佐々木元子, 由良敬, 高島響子, 李怡然, 神原容子, 松川愛未, 松川愛未, 大住理沙

    難病ゲノム医療に対応した遺伝カウンセリングの実態調査と教育システムの構築に資する研究 令和3年度 総括研究報告書(Web)    2022

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    三宅秀彦, 三宅秀彦, 小杉眞司, 櫻井晃洋, 川目裕, 松尾真理, 佐々木元子, 佐々木元子, 由良敬, 由良敬, 高島響子, 李怡然, 神原容子, 松川愛未, 大住理沙

    日本人類遺伝学会大会プログラム・抄録集   67th (CD-ROM)  2022

    J-GLOBAL

  • BRCA1バリアントのClinical Significanceとタンパク質相互作用情報との相関解析

    工藤美紗絵, 三宅秀彦, 三宅秀彦, 佐々木元子, 佐々木元子, 神原容子, 由良敬, 由良敬

    日本人類遺伝学会大会プログラム・抄録集   67th (CD-ROM)  2022

    J-GLOBAL

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    日本応用動物昆虫学会大会講演要旨   64th  2020

    J-GLOBAL

  • Engineering microbial rhodopsin without retinal-binding lysine to gain photosensitive function

    YAMAUCHI Yumeka, KONNO Masae, YAMADA Daichi, YAMADA Daichi, YURA Kei, YURA Kei, INOUE Keiichi, INOUE Keiichi, BEJA Oded, KANDORI Hideki

    生物物理(Web)   59 ( Supplement 1-2 )  2019

    J-GLOBAL

  • Comparative analysis of CpG island promoters between the human and rhesus monkey genomes

    Saki Auto, Mayu Fushimi, Kei Yura, Kohji Okamura

       2016  [Refereed]

    Research paper, summary (national, other academic conference)  

  • TafazzinトランスアシラーゼドメインにおけるBarth症候群関連変異と選択的スプライシングの構造および機能に対する影響

    土方 敦司, 由良 敬, 小原 收, 郷 通子

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [4T18p - 03(3P1259)]  2015.12

  • 緑藻植物門リン脂質:ジアシルグリセロールアシルトランスフェラーゼのホモロジーモデリングにもとづく機能発現機構の予測

    坂本美佳, 二河成男, 由良敬

    日本生化学会大会(Web)   88th   [2P0846] - [2P0846]  2015

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  • 29pAA-8 The Reaction mechanism and The Structure Stabilization Factor of The Active Site of DNA Photolyse

    Sato R., Kitoh-Nishioka H., Kawatsu T., Yura K., Ando K., Yamato T.

    Meeting abstracts of the Physical Society of Japan   69 ( 1 ) 415 - 415  2014.03

    CiNii

  • Visualization for Correlation between Druggability and Distance of Amino Acids in Protein Pockets

    Makiko Miyoshi, Takayuki Itoh, Kei Yura

    IPSJ SIG technical reports   2013 ( 1 ) 1 - 2  2013.09

     View Summary

    Protein is the major component of the organism. It has a unique three-dimensional structure determined by its amino acid sequence. A hole (pocket) on the surface of a protein is known to be the best target for a drug to react. We have started analyzing how "druggability" of proteins relates to the locations of amino acids in the pocket. For starter of the study, this paper presents a visualization tool for distance distribution analysis between two types of amino acids in the protein pocket. Providing protein surfaces by triangular meshes, this tool first identifies a pocket from the protein surface, specifies the deepest point in the pocket, and calculates distances between atoms of an amino acids and the deepest point of the pocket. The tool then visualizes the distribution of the distances by scatterplots. This paper presents a biological interpretation of the visualization results.

    CiNii

  • Distance Distribution Analysis in Pockets among Amino Acids

    MIYOSHI Makiko, ITOH Takayuki, YURA Kei

    ITE Technical Report   37 ( 17 ) 243 - 246  2013.03

     View Summary

    Protein is the major component of the organism. It has a unique typical three-dimensional structure determined by the sequence of, amino acids. A hole (pocket) on the surface of a protein is known to be the best target for a drug to react. We started analyzing how "druggability" of proteins related to the locations amino acids in a pocket. For a starter of this study, this paper presents a visualization tool for distance distribution analysis between two types of amino acids in a pocket. When protein surface is provided by triangular meshes, this tool first identifies a pocket from the protein surface, specifies the deepest position of the pockets, and calculates distances between atoms of an amino acid and the deepest positions of the pocket. This tool then visualizes the distribution of the distances by scatterplots. This paper proposes the a biological interpretation of the visualization results.

    CiNii

  • Roles of RNA Editing in Land Plant Organelles

    YURA Kei, GO Mitiko

    Seibutsu Butsuri   49 ( 5 ) 244 - 245  2009.09

    DOI CiNii

  • 理論計算+生命情報学で初めて見いだされた機能性残基―DNA 補修酵素の場合―

    倭 剛久, 西岡 宏任, 由良 敬

    生物物理   49 ( 4 ) 196 - 197  2009  [Invited]

    Article, review, commentary, editorial, etc. (scientific journal)  

  • ダイニン微小管結合部位の構造と機能

    加藤 有介, 八木 俊樹, 大木 進野, 由良 敬, 清水 洋輔, 本田 真也, 神谷 律, 田之倉 優

    バイオイメージング   17 ( 2 ) 204 - 205  2008.10

    CiNii

  • ダイニン微小管結合部位の構造と機能

    加藤 有介, 八木 俊樹, 大木 進野, 由良 敬, 清水 洋輔, 本田 真也, 神谷 律, 田之倉 優

    バイオイメージング   17 ( 2 ) 98 - 99  2008.10

    CiNii

  • 20pWE-2 Electron transfer reaction and function of DNA photolyase

    Yamato Takahisa, Nishioka Hirotaka, Yura Kei

    Meeting abstracts of the Physical Society of Japan   63 ( 2 ) 302 - 302  2008.08

    CiNii

  • S08I6 Alternative Splicing and Its Influence on Protein Conformation(Bioinformatics in the Era of Structural Proteomics)

    Go Mitiko, Yura Kei, Shionyu Masafumi

    Seibutsu Butsuri   47 ( 1 ) S12  2007.11

    DOI CiNii

  • Comparative analysis of ribosome atomic structures deduced computationally from EM images and X-ray structures

    Hisashi Ishida, Yu Tsutsumi, Atsushi Matsumoto, Kei Yura

    BIOPHYSICAL JOURNAL     508A - 508A  2007.01

    Research paper, summary (international conference)  

  • Structural analysis of ribosome based on the elastic network normal mode analysis

    Atsushi Matsumoto, Yu Tsutsumi, Kei Yura, Hisashi Ishida

    BIOPHYSICAL JOURNAL     508A - 508A  2007.01

    Research paper, summary (international conference)  

  • Coverage of whole proteome by structural genomics observed through protein homology modeling database

    Yura, K., Yamaguchi, A., Go, M.

    Journal of Structural and Functional Genomics   7 ( 2 ) 65 - 76  2006

     View Summary

    We have been developing FAMSBASE, a protein homology-modeling database of whole ORFs predicted from genome sequences. The latest update of FAMSBASE ( http://daisy.nagahama-i-bio.ac.jp/Famsbase/ ), which is based on the protein three-dimensional (3D) structures released by November 2003, contains modeled 3D structures for 368,724 open reading frames (ORFs) derived from genomes of 276 species, namely 17 archaebacterial, 130 eubacterial, 18 eukaryotic and 111 phage genomes. Those 276 genomes are predicted to have 734,193 ORFs in total and the current FAMSBASE contains protein 3D structure of approximately 50% of the ORF products. However, cases that a modeled 3D structure covers the whole part of an ORF product are rare. When portion of an ORF with 3D structure is compared in three kingdoms of life, in archaebacteria and eubacteria, approximately 60% of the ORFs have modeled 3D structures covering almost the entire amino acid sequences, however, the percentage falls to about 30% in eukaryotes. When annual differences in the number of ORFs with modeled 3D structure are calculated, the fraction of modeled 3D structures of soluble protein for archaebacteria is increased by 5%, and that for eubacteria by 7% in the last 3 years. Assuming that this rate would be maintained and that determination of 3D structures for predicted disordered regions is unattainable, whole soluble protein model structures of prokaryotes without the putative disordered regions will be in hand within 15 years. For eukaryotic proteins, they will be in hand within 25 years. The 3D structures we will have at those times are not the 3D structure of the entire proteins encoded in single ORFs, but the 3D structures of separate structural domains. Measuring or predicting spatial arrangements of structural domains in an ORF will then be a coming issue of structural genomics. © 2006 Springer Science+Business Media B.V.

    DOI PubMed

  • Amino acid residue doublet propensity in the protein-RNA interface and its application to RNA interface prediction

    Kim, O.T.P., Yura, K., Go, N.

    Nucleic Acids Research   34 ( 22 ) 6450 - 6460  2006

     View Summary

    Protein-RNA interactions play essential roles in a number of regulatory mechanisms for gene expression such as RNA splicing, transport, translation and post-transcriptional control. As the number of available protein-RNA complex 3D structures has increased, it is now possible to statistically examine protein-RNA interactions based on 3D structures. We performed computational analyses of 86 representative protein-RNA complexes retrieved from the Protein Data Bank. Interface residue propensity, a measure of the relative importance of different amino acid residues in the RNA interface, was calculated for each amino acid residue type (residue singlet interface propensity). In addition to the residue singlet propensity, we introduce a new residue-based propensity, which gives a measure of residue pairing preferences in the RNA interface of a protein (residue doublet interface propensity). The residue doublet interface propensity contains much more information than the sum of two singlet propensities alone. The prediction of the RNA interface using the two types of propensities plus a position-specific multiple sequence profile can achieve a specificity of about 80%. The prediction method was then applied to the 3D structure of two mRNA export factors, TAP (Mex67) and UAP56 (Sub2). The prediction enables us to point out candidate RNA interfaces, part of which are consistent with previous experimental studies and may contribute to elucidation of atomic mechanisms of mRNA export.

    DOI PubMed CiNii

  • Alternative splicing in human transcriptome: Functional and structural influence on proteins

    Yura, K., Shionyu, M., Hagino, K., Hijikata, A., Hirashima, Y., Nakahara, T., Eguchi, T., Shinoda, K., Yamaguchi, A., Takahashi, K.-i., Itoh, T., Imanishi, T., Gojobori, T., Go, M.

    Gene   380 ( 2 ) 63 - 71  2006

     View Summary

    Alternative splicing is a molecular mechanism that produces multiple proteins from a single gene, and is thought to produce variety in proteins translated from a limited number of genes. Here we analyzed how alternative splicing produced variety in protein structure and function, by using human full-length cDNAs on the assumption that all of the alternatively spliced mRNAs were translated to proteins. We found that the length of alternatively spliced amino acid sequences, in most cases, fell into a size shorter than that of average protein domain. We evaluated comprehensively the presumptive three-dimensional structures of the alternatively spliced products to assess the impact of alternative splicing on gene function. We found that more than half of the products encoded proteins which were involved in signal transduction, transcription and translation, and more than half of alternatively spliced regions comprised interaction sites between proteins and their binding partners, including substrates, DNA/RNA, and other proteins. Intriguingly, 67% of the alternatively spliced isoforms showed significant alterations to regions of the protein structural core, which likely resulted in large conformational change. Based on those findings, we speculate that there are a large number of cases that alternative splicing modulates protein networks through significant alteration in protein conformation. (c) 2006 Published by Elsevier B.V.

    DOI PubMed CiNii

  • Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs

    Takeda, J.-I., Suzuki, Y., Nakao, M., Barrero, R.A., Koyanagi, K.O., Jin, L., Motono, C., Hata, H., Isogai, T., Nagai, K., Otsuki, T., Kuryshev, V., Shionyu, M., Yura, K., Go, M., Thierry-Mieg, J., Thierry-Mieg, D., Wiemann, S., Nomura, N., Sugano, S., Gojobori, T., Iman ishi, T.

    Nucleic Acids Research   34 ( 14 ) 3917 - 3928  2006

     View Summary

    We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants.

    DOI PubMed

  • 2SE02 Roles of alternative splicing for diversification of protein structure and function

    Shionyu M., Yura K, Hijikata A., Nakahara T., Shinoda K., Yamaguchi A., Takahashi K., Go M.

    Seibutsu Butsuri   45 ( 1 ) S23  2005.10

    DOI CiNii

  • タンパク質フォールディング--自己組織化と遺伝子のスプライシングから迫る (Special Issue【特集】 DNA,タンパク質の自己組織化)

    郷 通子, 由良 敬

    バイオニクス   2 ( 1 ) 38 - 43  2005.01

    CiNii

  • 1P291 A knowledge-based trial to gain information for atomic resolution structures of supra-molecules out of their images by electron microscopy

    Yura K, Ishida H, Iwasaki K, Kawabata T, Tsutsumi Y, Matsumoto A, Mayanagi K

    Seibutsu Butsuri   45 ( 0 ) S104  2005

    DOI CiNii

  • 全ゲノムを対象とした蛋白質立体構造データベースの公開

    由良 敬, 山口晶太, 郷 通子

    蛋白質核酸酵素増刊号   50 ( 16 ) 2301 - 2301  2005

    CiNii

  • Sequence analysis of the gliding protein Gli349 in Mycoplasma mobile

    Metsugi Shoichi, Uenoyama Atsuko, Adan-Kubo Jun, Miyata Makoto, Yura Kei, Kono Hidetoshi, Go Nobuhiro

    BIOPHYSICS   1   33 - 43  2005

     View Summary

    The motile mechanism of Mycoplasma mobile remains unknown but is believed to differ from any previously identified mechanism in bacteria. Gli349 of M. mobile is known to be responsible for both adhesion to glass surfaces and mobility. We therefore carried out sequence analyses of Gli349 and its homolog MYPU2110 from M. pulmonis to decipher their structures. We found that the motif "YxxxxxGF" appears 11 times in Gli349 and 16 times in MYPU2110. Further analysis of the sequences revealed that Gli349 contains 18 repeats of about 100 amino acid residues each, and MYPU2110 contains 22. No sequence homologous to any of the repeats was found in the NCBI RefSeq non-redundant sequence database, and no compatible fold structure was found among known protein structures, suggesting that the repeat found in Gli349 and MYPU2110 is novel and takes a new fold structure. Proteolysis of Gli349 using chymotrypsin revealed that cleavage positions were often located between the repeats, implying that regions connecting repeats are unstructured, flexible and exposed to the solvent. Assuming that each repeat folds into a structural domain, we constructed a model of Gli349 that fits well the shape and size of images obtained with electron microscopy.<br>

    DOI CiNii

  • Newly sequenced eRF1s from ciliates: The diversity of stop codon usage and the molecular surfaces that are important for stop codon interactions

    Kim, O.T.P., Yura, K., Go, N., Harumoto, T.

    Gene   346   277 - 286  2005

     View Summary

    The genetic code of nuclear genes in some ciliates was found to differ from that of other organisms in the assignment of UGA, UAG, and UAA codons, which are normally assigned as stop codons. In some ciliate species, the universal stop codons UAA and UAG instead encode glutamine. In some other ciliates, the universal stop codon UGA appears to be translated as cysteine or tryptophan. Eukaryotic release factor 1 (eRF1) is a key protein, in stop codon recognition, thus, the protein is believed to play an important role in the stop codon reassignment in ciliates. We have cloned, sequenced, and analyzed the cDNA of eRF1 from four ciliate species of three different classes: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Phylogenetic analysis of these eRF1s supports the hypothesis that the genetic code in ciliates has deviated independently several times from the universal genetic code, and that different ciliate eRF1s may have undergone different processes to change the codon specificity. Using computational methods, we have also suggested areas on the surface of eRF1s that are important for stop codon recognition in ciliate eRF1s. (c) 2004 Elsevier B.V. All rights reserved.

    DOI PubMed CiNii

  • 3P283 Effects of alternative splicing on protein 3D structures

    Shionyu M., Yura K., Hagino K., Hijikata A., Hiroshima Y., Nakahara T., Eguchi T., Shinoda K., Yamaguchi A., Takahashi K., Itoh T., Imanishi T., Gojobori T., Go M.

    Seibutsu Butsuri   44 ( 1 ) S260  2004.11

    DOI CiNii

  • 3P284 Extended search tools in Het-PDB Navi. : A database of interactions between proteins and small molecules

    Yamaguchi A., Tomoda S., Yura K., Go M.

    Seibutsu Butsuri   44 ( 1 ) S260  2004.11

    DOI CiNii

  • Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates (vol 51, pg 227, 2004)

    OTP Kim, K Yura, N Go, T Harumoto

    JOURNAL OF EUKARYOTIC MICROBIOLOGY   51 ( 4 ) 495 - 495  2004.07

    Other  

  • Integrative annotation of 21,037 human genes validated by full-length cDNA clones

    T Imanishi, T Itoh, Y Suzuki, C O'Donovan, S Fukuchi, KO Koyanagi, RA Barrero, T Tamura, Y Yamaguchi-Kabata, M Tanino, K Yura, S Miyazaki, K Ikeo, K Homma, A Kasprzyk, T Nishikawa, M Hirakawa, J Thierry-Mieg, D Thierry-Mieg, J Ashurst, LB Jia, M Nakao, MA Thomas, N Mulder, Y Karavidopoulou, LH Jin, S Kim, T Yasuda, B Lenhard, E Eveno, Y Suzuki, C Yamasaki, J Takeda, C Gough, P Hilton, Y Fujii, H Sakai, S Tanaka, C Amid, M Bellgard, MD Bonaldo, H Bono, SK Bromberg, AJ Brookes, E Bruford, P Carninci, C Chelala, C Couillault, SJ de Souza, MA Debily, MD Devignes, Dubchak, I, T Endo, A Estreicher, E Eyras, K Fukami-Kobayash, GR Gopinath, E Graudens, Y Hahn, M Han, ZG Han, K Hanada, H Hanaoka, E Harada, K Hashimoto, U Hinz, M Hirai, T Hishiki, Hopkinson, I, S Imbeaud, H Inoko, A Kanapin, Y Kaneko, T Kasukawa, J Kelso, P Kersey, R Kikuno, K Kimura, B Korn, Kuryshev, V, Makalowska, I, T Makino, S Mano, R Mariage-Samson, J Mashima, H Matsuda, HW Mewes, S Minoshima, K Nagai, H Nagasaki, N Nagata, R Nigam, O Ogasawara, O Ohara, M Ohtsubo, N Okada, T Okido, S Oota, M Ota, T Ota, T Otsuki, D Piatier-Tonneau, A Poustka, SX Ren, N Saitou, K Sakai, S Sakamoto, R Sakate, Schupp, I, F Servant, S Sherry, R Shiba, N Shimizu, M Shimoyama, AJ Simpson, B Soares, C Steward, M Suwa, M Suzuki, A Takahashi, G Tamiya, H Tanaka, T Taylor, JD Terwilliger, P Unneberg, Veeramachaneni, V, S Watanabe, L Wilming, N Yasuda, HS Yoo, M Stodolsky, W Makalowski, M Go, K Nakai, T Takagi, M Kanehisa, Y Sakaki, J Quackenbush, Y Okazaki, Y Hayashizaki, W Hide, R Chakraborty, K Nishikawa, H Sugawara, Y Tateno, Z Chen, M Oishi, P Tonellato, R Apweiler, K Okubo, L Wagner, S Wiemann, RL Strausberg, T Isogai, C Auffray, N Nomura, T Gojobori, S Sugano

    PLOS BIOLOGY   2 ( 6 ) 856 - 875  2004.06

    Book review, literature introduction, etc.  

     View Summary

    The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for nonprotein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

    DOI

  • Highly divergent actins from karyorelictean, heterotrich, and litostome ciliates (vol 51, pg 227, 2004)

    OTP Kim, K Yura, N Go, T Harumoto

    JOURNAL OF EUKARYOTIC MICROBIOLOGY   51 ( 3 ) 338 - 338  2004.05

    Other  

  • 28aYE-8 Genome Function Prediction Based on Transcription Systems

    Yura K., Kono H., Go N.

    Meeting abstracts of the Physical Society of Japan   59 ( 1 ) 366 - 366  2004.03

    CiNii

  • Highly divergent actins from Karyorelictean, Heterotrich, and Litostome Ciliates

    Oanh T. P. Kim, Kei Yura, G. O. Nobuhiro, Terue Harumoto

    Journal of Eukaryotic Microbiology   51 ( 2 ) 227 - 233  2004.03

     View Summary

    We have cloned, sequenced, and characterized cDNA of actins from five ciliate species of three different classes of the phylum Ciliophora: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma japonicum, Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Loxodes striatus uses UGA as the stop codon and has numerous in-frame UAA and UAG, which are translated into glutamine. The other four species use UAA as the stop codon and have no in-frame UAG nor UGA. The putative amino acid sequences of the newly determined actin genes were found to be highly divergent as expected from previous findings of other ciliate actins. These sequences were also highly divergent from other ciliate actins, indicating that actin genes are highly diverse even within the phylum Ciliophora. Phylogenetic analysis showed high evolutionary rate of ciliate actins. Our results suggest that the evolutionary rate was accelerated because of the differences in molecular interactions.

    DOI PubMed

  • ビタミン、ミネラルのかたち 「食品の科学」 (上野川修一、田之倉優 編集)

    東京化学同人    2004.02

     View Summary

    2004.2予定

  • Het-PDB Navi.: A database for protein-small molecule interactions

    A Yamaguchi, K Iida, N Matsui, S Tomoda, K Yura, M Go

    JOURNAL OF BIOCHEMISTRY   135 ( 1 ) 79 - 84  2004.01

     View Summary

    The genomes of more than 100 species have been sequenced, and the biological functions of encoded proteins are now actively being researched. Protein function is based on interactions between proteins and other molecules. One approach to assuming protein function based on genomic sequence is to predict interactions between an encoded protein and other molecules. As a data source for such predictions, knowledge regarding known protein-small molecule interactions needs to be compiled. We have, therefore, surveyed interactions between proteins and other molecules in Protein Data Bank (PDB), the protein three-dimensional (3D) structure database. Among 20,685 entries in PDB (April, 2003), 4,189 types of small molecules were found to interact with proteins. Biologically relevant small molecules most often found in PDB were metal ions, such as calcium, zinc, and magnesium. Sugars and nucleotides were the next most common. These molecules are known to act as cofactors for enzymes and/or stabilizers of proteins. In each case of interactions between a protein and small molecule, we found preferred amino acid residues at the interaction sites. These preferences can be the basis for predicting protein function from genomic sequence and protein 3D structures. The data pertaining to these small molecules were collected in a database named Het-PDB Navi., which is freely available at http:// daisy.nagahama-i-bio.ac.jp/golab/hetpdbnavi.html and linked to the official PDB home page.

    DOI

  • Highly divergent actins from Karyorelictean, Heterotrich, and Litostome Ciliates

    Kim, O.T.P., Yura, K., Nobuhiro, G.O., Harumoto, T.

    Journal of Eukaryotic Microbiology   51 ( 2 ) 227 - 233  2004

     View Summary

    We have cloned, sequenced, and characterized cDNA of actins from five ciliate species of three different classes of the phylum Ciliophora: Karyorelictea (Loxodes striatus), Heterotrichea (Blepharisma japonicum, Blepharisma musculus), and Litostomatea (Didinium nasutum, Dileptus margaritifer). Loxodes striatus uses UGA as the stop codon and has numerous in-frame UAA and UAG, which are translated into glutamine. The other four species use UAA as the stop codon and have no in-frame UAG nor UGA. The putative amino acid sequences of the newly determined actin genes were found to be highly divergent as expected from previous findings of other ciliate actins. These sequences were also highly divergent from other ciliate actins, indicating that actin genes are highly diverse even within the phylum Ciliophora. Phylogenetic analysis showed high evolutionary rate of ciliate actins. Our results suggest that the evolutionary rate was accelerated because of the differences in molecular interactions.

    DOI PubMed

  • Het-PDB Navi.: A database for protein-small molecule interactions

    A Yamaguchi, K Iida, N Matsui, S Tomoda, K Yura, M Go

    JOURNAL OF BIOCHEMISTRY   135 ( 1 ) 79 - 84  2004.01

     View Summary

    The genomes of more than 100 species have been sequenced, and the biological functions of encoded proteins are now actively being researched. Protein function is based on interactions between proteins and other molecules. One approach to assuming protein function based on genomic sequence is to predict interactions between an encoded protein and other molecules. As a data source for such predictions, knowledge regarding known protein-small molecule interactions needs to be compiled. We have, therefore, surveyed interactions between proteins and other molecules in Protein Data Bank (PDB), the protein three-dimensional (3D) structure database. Among 20,685 entries in PDB (April, 2003), 4,189 types of small molecules were found to interact with proteins. Biologically relevant small molecules most often found in PDB were metal ions, such as calcium, zinc, and magnesium. Sugars and nucleotides were the next most common. These molecules are known to act as cofactors for enzymes and/or stabilizers of proteins. In each case of interactions between a protein and small molecule, we found preferred amino acid residues at the interaction sites. These preferences can be the basis for predicting protein function from genomic sequence and protein 3D structures. The data pertaining to these small molecules were collected in a database named Het-PDB Navi., which is freely available at http:// daisy.nagahama-i-bio.ac.jp/golab/hetpdbnavi.html and linked to the official PDB home page.

    DOI

  • Novel types of two-domain multi-copper oxidases: possible missing links in the evolution

    K Nakamura, T Kawabata, K Yura, N Go

    FEBS LETTERS   553 ( 3 ) 239 - 244  2003.10

     View Summary

    An analysis of the genome sequence database revealed novel types of two-domain multi-copper oxidases. The two-domain proteins have the conspicuous combination of blue-copper and inter-domain trinuclear copper binding residues, which is common in ceruloplasmin and ascorbate oxidase but not in nitrite reductase, and therefore are considered to retain the characteristics of the plausible ancestral form of ceruloplasmin and ascorbate oxidase. A possible evolutionary relationship of these proteins is proposed. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI PubMed CiNii

  • A database of interactions between proteins and small molecules

    Yamaguchi A., Tomoda S., Yura K., Go M.

    Seibutsu Butsuri   43 ( 1 ) S214  2003.08

    DOI CiNii

  • Prediction of specificity determinants of an enzyme : A test case on fungi peroxidases

    Yura K., Go M.

    Seibutsu Butsuri   43 ( 1 ) S214  2003.08

    DOI CiNii

  • 名古屋大学にて公開しているFAMSBASEについて

    由良 敬, 郷 通子

    生物物理   43 ( 2 ) 63 - 63  2003.03

    CiNii

  • バイオインフォマティクスが追い求めるもの

    由良 敬

    名古屋大学情報連携基盤センターニュース   3 ( 2 ) 136 - 143  2003

    CiNii

  • Enlarged FAMSBASE: Protein 3D structure models of genome sequences for 41 species

    Yamaguchi, A., Iwadate, M., Suzuki, E.-I., Yura, K., Kawakita, S., Umeyama, H., Go, M.

    Nucleic Acids Research   31 ( 1 ) 463 - 468  2003

     View Summary

    Enlarged FAMSBASE is a relational database of comparative protein structure models for the whole genome of 41 species, presented in the GTOP database. The models are calculated by Full Automatic Modeling System ( FAMS). Enlarged FAMSBASE provides a wide range of query keys, such as name of ORF ( open reading frame), ORF keywords, Protein Data Bank ( PDB) ID, PDB heterogen atoms and sequence similarity. Heterogen atoms in PDB include cofactors, ligands and other factors that interact with proteins, and are a good starting point for analyzing interactions between proteins and other molecules. The data may also work as a template for drug design. The present number of ORFs with protein 3D models in FAMSBASE is 183 805, and the database includes an average of three models for each ORF. FAMSBASE is available at http: / / famsbase. bio. nagoya- u. ac. jp/ famsbase/

    DOI PubMed CiNii

  • タンパク質立体構造の進化「ゲノムからみた生物の多様性と進化」 (五條堀孝 編集)

    シュプリンガー・フェアラーク   33-40  2003

  • Enlarged FAMSBASE: protein 3D structure models of genome sequences for 41 species

    A Yamaguchi, M Iwadate, E Suzuki, K Yura, S Kawakita, H Umeyama, M Go

    NUCLEIC ACIDS RESEARCH   31 ( 1 ) 463 - 468  2003.01

     View Summary

    Enlarged FAMSBASE is a relational database of comparative protein structure models for the whole genome of 41 species, presented in the GTOP database. The models are calculated by Full Automatic Modeling System ( FAMS). Enlarged FAMSBASE provides a wide range of query keys, such as name of ORF ( open reading frame), ORF keywords, Protein Data Bank ( PDB) ID, PDB heterogen atoms and sequence similarity. Heterogen atoms in PDB include cofactors, ligands and other factors that interact with proteins, and are a good starting point for analyzing interactions between proteins and other molecules. The data may also work as a template for drug design. The present number of ORFs with protein 3D models in FAMSBASE is 183 805, and the database includes an average of three models for each ORF. FAMSBASE is available at http: / / famsbase. bio. nagoya- u. ac. jp/ famsbase/

    DOI PubMed CiNii

  • Novel types of two-domain multi-copper oxidases: Possible missing links in the evolution

    Nakamura, K., Kawabata, T., Yura, K., Go, N.

    FEBS Letters   553 ( 3 ) 239 - 244  2003

     View Summary

    An analysis of the genome sequence database revealed novel types of two-domain multi-copper oxidases. The two-domain proteins have the conspicuous combination of blue-copper and inter-domain trinuclear copper binding residues, which is common in ceruloplasmin and ascorbate oxidase but not in nitrite reductase, and therefore are considered to retain the characteristics of the plausible ancestral form of ceruloplasmin and ascorbate oxidase. A possible evolutionary relationship of these proteins is proposed. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI PubMed CiNii

  • データベース構築と構造バイオインフォマティクス モジュールに基づくゲノム機能予測--3Dキーノート (蛋白質ネットワークの構造生物学) -- (第2部 構造プロテオミクスにおける最新技術)

    由良 敬, 郷 通子

    蛋白質核酸酵素   47 ( 8 ) 1090 - 1096  2002.06

    CiNii

  • モジュールに基づくゲノム機能予測 蛋白質核酸酵素増刊「構造プロテオミクス」

    共立出版   ( 47 ) 1090 - 1096  2002

  • ゲノム配列にもとづくタンパク質機能予測 「プロテオミクスの最新技術」深見泰夫監修

    ジーエムシー出版   93-101  2002

  • Module organization and origin of myoglobin

    Shionyu M., Yura K., Go M.

    Seibutsu Butsuri   41 ( 1 ) S21  2001.09

    DOI CiNii

  • ORF function prediction by module 3D-keynote : In case of cyanobacterium genome

    Yura K., Go M.

    Seibutsu Butsuri   41 ( 1 ) S80  2001.09

    DOI CiNii

  • Mutational analysis of genes involved in pilus structure, motility and transformation competency in the unicellular motile cyanobacterium Synechocystis sp PCC 6803

    S Yoshihara, XX Geng, S Okamoto, K Yura, T Murata, M Go, M Ohmori, M Ikeuchi

    PLANT AND CELL PHYSIOLOGY   42 ( 1 ) 63 - 73  2001.01

     View Summary

    The relevance of pilus-related genes to motility, pilus structure on the cell surface and competency of natural transformation was studied by gene disruption analysis in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803. The genes disrupted in this study were chosen as related to the pil genes for biogenesis of the type IV pill in a Gram-negative bacterium Pseudomonas aeruginosa, It was found that motility of Synechocystis cells was lost in the mutants of slr0063, slr1274, slr1275, slr1276, slr1277 and sll1694 together with a simultaneous loss of the thick pill on the cell surface. Competency of the natural transformation was lost in the mutants listed above and slr0197-disruptant. The gene slr0197 was previously predicted as a competence gene by a search with sequence-independent DNA-binding structure [Yura et al. (1999) DNA Res. 6: 75]. It was suggested that both DNA uptake for natural transformation and motility are mediated by a specific type IV-like pilus structure, while a putative DNA-binding protein encoded by slr0197 is additionally required for the DNA uptake. Based on the homology with the pil genes in P. aeruginosa, slr0063, slr1274, slr1275, slr1276, slr1277 and sll1694 were designated pilB1, pilM, pilN, pilO, pilQ and pilA1, respectively. The gene slr0197 was designated comA.

    DOI PubMed CiNii

  • Capacity of thermomonospora alba Xy1A to impart thermostability in family F/10 chimeric xylanases

    Ahsan, M.M., Kaneko, S., Wang, Q., Yura, K., Go, M., Hayash, K.

    Enzyme and Microbial Technology   28 ( 1 ) 8 - 15  2001

     View Summary

    To reveal structure-function relationships of family F/10 glycanases, an in vitro molecular level shuffling experiment was conducted to accumulate useful amino acid residues from two homologous F/10 xylanases, FXYN of Streptomyces olivaceoviridis E-86 and XylA of Thermomonospora alba ULJB1, into a single chimeric xylanase. The parent genes were shuffled by crossovers at selected module borders using self-priming Polymerase Chain Reaction (PCR)s. The shuffled constructs, designated as FXYN-M3/4-XylA, FXYN-M9/10-XylA, and FXYN-M14/15-XylA were cloned and their nucleotide sequences were confirmed. Two chimera, FXYN-M3/4-XylA and FXYN-M14/15-XylA, demonstrated activity against RBB-xylan and were over-expressed as His-tag fusion proteins under control of T5 promoter of pQE60. The homogeneously pure chimeric proteins, FXYN-M3/4-XylA and FXYN-M14/15-XylA showed improved thermal and pH profiles compared to those of one of the parents, FXYN. This was apparently due to the influence of amino acids inherited from thermophilic XylA. Measured K-m and kcat values were closer to those of the other parent, XylA. Interestingly, a significant level of heat tolerance up to 60 degreesC, was recorded for FXYN-M3/4-XylA in comparison to only 40 degreesC for FXYN-M14/15-XylA though their temperature optima did not correlates with their thermal stability. These results indicated that the amino acid residues of the larger T. alba XylA DNA fragment present in FXYN-M3/4-XylA were responsible for inducing its thermal stability. (C) 2001 Elsevier Science Inc. All rights reserved.

    DOI PubMed CiNii

  • ジンクフィンガードメイン.「生体の化学:モチーフ・ドメインリスト」金原一郎記念医学医療振興財団

    医学書院   394-395  2001

  • POUドメイン. 「生体の化学:モチーフ・ドメインリスト」金原一郎記念医学医療振興財団

    医学書院   384-385  2001

  • Mutational analysis of genes involved in pilus structure, motility and transformation competency in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803

    Yoshihara, S., Geng, X.X., Okamoto, S., Yura, K., Murata, T., Go, M., Ohmori, M., Ikeuchi, M.

    Plant and Cell Physiology   42 ( 1 ) 63 - 73  2001

     View Summary

    The relevance of pilus-related genes to motility, pilus structure on the cell surface and competency of natural transformation was studied by gene disruption analysis in the unicellular motile cyanobacterium Synechocystis sp. PCC 6803. The genes disrupted in this study were chosen as related to the pil genes for biogenesis of the type IV pill in a Gram-negative bacterium Pseudomonas aeruginosa, It was found that motility of Synechocystis cells was lost in the mutants of slr0063, slr1274, slr1275, slr1276, slr1277 and sll1694 together with a simultaneous loss of the thick pill on the cell surface. Competency of the natural transformation was lost in the mutants listed above and slr0197-disruptant. The gene slr0197 was previously predicted as a competence gene by a search with sequence-independent DNA-binding structure [Yura et al. (1999) DNA Res. 6: 75]. It was suggested that both DNA uptake for natural transformation and motility are mediated by a specific type IV-like pilus structure, while a putative DNA-binding protein encoded by slr0197 is additionally required for the DNA uptake. Based on the homology with the pil genes in P. aeruginosa, slr0063, slr1274, slr1275, slr1276, slr1277 and sll1694 were designated pilB1, pilM, pilN, pilO, pilQ and pilA1, respectively. The gene slr0197 was designated comA.

    DOI PubMed CiNii

  • Capacity of thermomonospora alba XylA to impart thermostability in family F/10 chimeric xylanases

    MM Ahsan, S Kaneko, Q Wang, K Yura, M Go, K Hayash

    ENZYME AND MICROBIAL TECHNOLOGY   28 ( 1 ) 8 - 15  2001.01

     View Summary

    To reveal structure-function relationships of family F/10 glycanases, an in vitro molecular level shuffling experiment was conducted to accumulate useful amino acid residues from two homologous F/10 xylanases, FXYN of Streptomyces olivaceoviridis E-86 and XylA of Thermomonospora alba ULJB1, into a single chimeric xylanase. The parent genes were shuffled by crossovers at selected module borders using self-priming Polymerase Chain Reaction (PCR)s. The shuffled constructs, designated as FXYN-M3/4-XylA, FXYN-M9/10-XylA, and FXYN-M14/15-XylA were cloned and their nucleotide sequences were confirmed. Two chimera, FXYN-M3/4-XylA and FXYN-M14/15-XylA, demonstrated activity against RBB-xylan and were over-expressed as His-tag fusion proteins under control of T5 promoter of pQE60. The homogeneously pure chimeric proteins, FXYN-M3/4-XylA and FXYN-M14/15-XylA showed improved thermal and pH profiles compared to those of one of the parents, FXYN. This was apparently due to the influence of amino acids inherited from thermophilic XylA. Measured K-m and kcat values were closer to those of the other parent, XylA. Interestingly, a significant level of heat tolerance up to 60 degreesC, was recorded for FXYN-M3/4-XylA in comparison to only 40 degreesC for FXYN-M14/15-XylA though their temperature optima did not correlates with their thermal stability. These results indicated that the amino acid residues of the larger T. alba XylA DNA fragment present in FXYN-M3/4-XylA were responsible for inducing its thermal stability. (C) 2001 Elsevier Science Inc. All rights reserved.

    DOI PubMed CiNii

  • Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis

    H Kikuchi, H Wako, K Yura, M Go, M Mimuro

    BIOPHYSICAL JOURNAL   79 ( 3 ) 1587 - 1600  2000.09

     View Summary

    Phycobiliproteins are basic building blocks of phycobilisomes, a supra-molecular assembly for the light-capturing function of photosynthesis in cyanobacteria and red algae. One functional form of phycobiliproteins is a trimeric form consisting of three identical units having C-3 symmetry, with each unit composed of two kinds of subunits, the alpha-subunit and beta-subunit. These subunits have similar chain folds and can be divided into either globin-like or X-Y helices domains. We studied the significance of this two-domain structure for their assembled structures and biological function (light-absorption) using a normal mode analysis to investigate dynamic aspects of their three-dimensional structures. We used C-phycocyanin (C-PC) as an example, and focused on the interactions between the two domains. The normal mode analysis was carried out for the following two cases: 1) the whole subunit, including the two domains; and 2) the globin-like domain alone. By comparing the dynamic properties, such as correlative movements between residues and the fluctuations of individual residues, we found that the X-Y helices domain plays an important role not only in the C-3 symmetry assemblies of the subunits in phycobiliproteins, but also in stabilizing the light absorption property by suppressing the fluctuation of the specific Asp residues near the chromophore. Interestingly, the conformation of the X-Y helices domain corresponds to that of a module in pyruvate phosphate dikinase (PPDK). The module in PPDK is involved in the interactions of two domains, just as the X-Y helices domain is involved in the interactions of two subunits. Finally, we discuss the mechanical construction of the C-PC subunits based on the normal mode analysis.

  • Genome function prediction based on protein modules

    Yura K., Go M

    Seibutsu Butsuri   40 ( 1 ) S106  2000.08

    DOI CiNii

  • Localization of Ca-, Zn-and Mg-ligands to a limited number of modules

    Iida K., Matsui N., Yura K, Go M.

    Seibutsu Butsuri   40 ( 1 ) S195  2000.08

    DOI CiNii

  • タンパク質立体構造に基づくゲノム機能予測.「ゲノム情報生物学-bio-informaticsとinformation biology」(松原謙一、榊 佳之 監修)

    中山書店     100 - 115  2000

  • Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.: Module shuffling of a family F/10 xylanase: replacement of modules M4 and M5 of the FXYN of Streptomyces oliva・・・

    <i>Protein Engng</i>   ( 13 ) 873 - 879  2000

     View Summary

    Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.: Module shuffling of a family F/10 xylanase: replacement of modules M4 and M5 of the FXYN of Streptomyces olivaceviridis E-86 with those of the Cex of Cellulomonas fimi.

  • Significance of a two-domain structure in subunits of phycobiliproteins revealed by the normal mode analysis

    Kikuchi, H., Wako, H., Yura, K., Go, M., Mimuro, M.

    Biophysical Journal   79 ( 3 ) 1587 - 1600  2000

     View Summary

    Phycobiliproteins are basic building blocks of phycobilisomes, a supra-molecular assembly for the light-capturing function of photosynthesis in cyanobacteria and red algae. One functional form of phycobiliproteins is a trimeric form consisting of three identical units having C-3 symmetry, with each unit composed of two kinds of subunits, the alpha-subunit and beta-subunit. These subunits have similar chain folds and can be divided into either globin-like or X-Y helices domains. We studied the significance of this two-domain structure for their assembled structures and biological function (light-absorption) using a normal mode analysis to investigate dynamic aspects of their three-dimensional structures. We used C-phycocyanin (C-PC) as an example, and focused on the interactions between the two domains. The normal mode analysis was carried out for the following two cases: 1) the whole subunit, including the two domains; and 2) the globin-like domain alone. By comparing the dynamic properties, such as correlative movements between residues and the fluctuations of individual residues, we found that the X-Y helices domain plays an important role not only in the C-3 symmetry assemblies of the subunits in phycobiliproteins, but also in stabilizing the light absorption property by suppressing the fluctuation of the specific Asp residues near the chromophore. Interestingly, the conformation of the X-Y helices domain corresponds to that of a module in pyruvate phosphate dikinase (PPDK). The module in PPDK is involved in the interactions of two domains, just as the X-Y helices domain is involved in the interactions of two subunits. Finally, we discuss the mechanical construction of the C-PC subunits based on the normal mode analysis.

    DOI

  • Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.: Module shuffling of a family F/10 xylanase: replacement of modules M4 and M5 of the FXYN of Streptomyces oliva・・・

    <i>Protein Engng.</i>   ( 13 ) 873 - 879  2000

     View Summary

    Kaneko, S., Iwamatsu, S., Kuno, A., Fujimoto, Z., Sato, Y., Yura, K., Go, M., Mizuno, H., Taira, K., Hasegawa, T., Kusakabe, I., Hayashi, K.: Module shuffling of a family F/10 xylanase: replacement of modules M4 and M5 of the FXYN of Streptomyces olivaceviridis E-86 with those of the Cex of Cellulomonas fimi.

  • 3D-keynote for structurally and functionally similar pbHTH modules.

    Yura K., Toh H., Go M.

    Seibutsu Butsuri   39 ( 1 ) S130  1999.09

    DOI CiNii

  • Dynamical properties of prion protein C-terminal domain.

    Shinoda K., Yura K., Go M.

    Seibutsu Butsuri   39 ( 1 ) S130  1999.09

    DOI CiNii

  • Module-intron correlation and intron sliding in family F/10 xylanase genes

    Y Sato, Y Niimura, K Yura, M Go

    GENE   238 ( 1 ) 93 - 101  1999.09

     View Summary

    Xylanases are classified into two families, numbered F/10 and G/11 according to the similarity of amino acid sequences of their catalytic domain (Henrissat, B., Bairoch, A., 1993. New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem. J. 293, 781-788). Three-dimensional structure of the catalytic domain of the family F/10 xylanase was reported (White, A., Withers, S.G., Gilkes, N.R., Rose, D.R., 1994. Crystal structure of the catalytic domain of the beta-1,4-glycanase Cex from Cellulomonas fimi. Biochemistry 33, 12546-12552). The domain was decomposed into 22 modules by centripetal profiles (Gb, M., Nosaka, M., 1987. Protein architecture and the origin of introns. Cold Spring Harbor Symp. Quant. Biol. 52, 915-924; Noguti, T., Sakakibara, H., Gb, M., 1993. Localization of hydrogen-bonds within modules in barnase. Proteins 16, 357-363). A module is a contiguous polypeptide segment of amino acid residues having a compact conformation within a globular domain. Collected 31 intron sites of the family F/10 xylanase genes from fungus were found to be correlated to module boundaries with considerable statistical force (p values &lt;0.001). The relationship between the intron locations and protein structures provides supporting evidence for the ancient origin of introns, because such a relationship cannot be expected by random insertion of introns into eukaryotic genes, but it rather suggests pre-existence of introns in the ancestral genes of prokaryotes and eukaryotes. A phylogenetic tree of the fungal and bacterial xylanase sequences made two clusters; one includes both the bacterial and fungal genes, but the other consists of only fungal genes. The mixed cluster of bacterial genes without introns and the fungal genes with introns further supports the ancient origin of introns. Comparison of the conserved base sequences of introns indicates that sliding of a splice site occurred in Aspergillus kawachii gene by one base from the ancestral position. Substrate-binding sites of xylanase are localized on eight modules, and introns are found at both termini of six out of these functional modules. This result suggests that introns might play a functional role in shuffling the exons encoding the substrate-binding modules. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI

  • Repetitive use of a phosphate-binding module in DNA polymerase beta, Oct-1 POU domain and phage repressors

    K Yura, M Shionyu, K Kawatani, M Go

    CELLULAR AND MOLECULAR LIFE SCIENCES   55 ( 3 ) 472 - 486  1999.03

     View Summary

    Motifs for sequence specific-protein-DNA interactions, such as helix-turn-helix, zinc finger and leucine zipper, are now better understood as a result of extensive studies of three-dimensional (3D) structures of transcription factors. On the other hand, little attention has been paid to motifs for sequence nonspecific binding, namely DNA-phosphate binding. To address the question whether different transcription factors and DNA manipulation enzymes, that is enzymes that work on DNA, share a similar mode of phosphate binding, we sun eyed interactions between DNA and protein module, a structural unit of a globular protein. We analyzed the modular organization of DNA polymerase beta and found that residues making contact with DNA phosphates were localized to five modules. Structural comparison of these phosphate-binding modules against others in transcription factors and DNA manipulation enzymes revealed that DNA polymerase beta. the oct-1 POU domain, 434 Cro and the Are repressor have a phosphate-binding module with 3D structures similar to one another, This newly detected module, the phosphate-binding helix-turn-helix (pbHTH) module, named for its function and 3D structure, interacts with DNA by (i) making hydrogen bonds between a DNA phosphodiester oxygen and an amino hydrogen of the main chain located at the N-terminus of a C-terminal alpha-helix. and (ii) making electrostatic interactions between DNA phosphates and side chains of lysine or arginine. Finding structurally and functionally similar phosphate-binding units in different transcription factors and DNA manipulation enzymes suggests that shuffling of modules is not limited to the DNA base-recognition motif. Phosphate-binding modules are apparently also shuffled in DNA-binding proteins.

    DOI PubMed CiNii

  • Putative mechanism of natural transformation as deduced from genome data

    Yura, K., Toh, H., Go, M.

    DNA Research   6 ( 2 ) 75 - 82  1999

     View Summary

    Genetic transformation is widely utilized in molecular biology as a tool for gene cloning in Escherichia coli and for gene mapping in Bacillus subtilis. Several strains of eubacteria can naturally take up exogenous DNA and integrate the DNA into their own genomes. Molecular details of natural transformation, however, remained to be elucidated. The complete genome of a cyanobacterium, Synechocystis sp. PCC6803, has been sequenced. This bacterium has been used to examine functions of a particular gene. The genome is considered to carry information on natural transformable characteristics of Synechocystis. The first step in genetic transformation is the uptake of exogenous DNA. Proteins with non-specific DNA binding features are required, because specificity in the exogenous DNA has not been demonstrated. Such proteins have modules interacting with the phosphate backbone of DNA, including helix-turn-helix modules. Using a consensus pattern of the phosphate-binding helix-turn-helix module, we searched through the genome data of Synechocystis for genes or open reading frame (ORF) products with the pattern in primary structures. We found that an ORF, slr0197, has the pattern in duplicate at the C-terminal region. We also found that the ORF product has a hydrophobic segment at the N-terminal region, which is followed by two internal repeats of the endonuclease domain. Based on these observations, we propose a model for the initial stage of genetic transformation. This is apparently the first report on molecular mechanisms of natural transformation.

    DOI PubMed CiNii

  • Kaneko, S., Kuno, A., Fujimoto, Z., Shimizu, D., Machida, S., Sato, Y., Yura, K., Go, M.,Mizuno, H., Taira, K., Kusakabe, I. and Hayashi, K.: An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivac・・・

    <i>FEBS letters</i>   ( 460 ) 61 - 66  1999

     View Summary

    Kaneko, S., Kuno, A., Fujimoto, Z., Shimizu, D., Machida, S., Sato, Y., Yura, K., Go, M.,Mizuno, H., Taira, K., Kusakabe, I. and Hayashi, K.: An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivaceoviridis E-86 by module shuffling with the Cex of Cellulomonas fimi and by site-directed mutagenesis.

    DOI

  • Go, M. and Yura, K.: Protein Folding and Genome Evolution in "Old and New Views of Protein Folding(eds. Kuwajima, K. and Arai, M.)

    Elsevier     239 - 248  1999

  • Yura, K., Shionyu, M., Kawatani, K. and Go, M.: Repetitive use of a phosphate-bindig module in DNA polymerase beta, Oct-1 POU domain and phage repressors.

    <i>Cellular and Molecular Life Sciences</i>   55 ( 3 ) 472 - 486  1999

    DOI PubMed CiNii

  • Putative mechanism of natural transformation as deduced from genome data

    Kei Yura, Hiroyuki Toh, Mitiko Go

    DNA Research   6 ( 2 ) 75 - 82  1999

     View Summary

    Genetic transformation is widely utilized in molecular biology as a tool for gene cloning in Escherichia coli and for gene mapping in Bacillus subtilis. Several strains of eubacteria can naturally take up exogenous DNA and integrate the DNA into their own genomes. Molecular details of natural transformation, however, remained to be elucidated. The complete genome of a cyanobacterium, Synechocystis sp. PCC6803, has been sequenced. This bacterium has been used to examine functions of a particular gene. The genome is considered to carry information on natural transformable characteristics of Synechocystis. The first step in genetic transformation is the uptake of exogenous DNA. Proteins with non-specific DNA binding features are required, because specificity in the exogenous DNA has not been demonstrated. Such proteins have modules interacting with the phosphate backbone of DNA, including helix-turn-helix modules. Using a consensus pattern of the phosphate-binding helix-turn-helix module, we searched through the genome data of Synechocystis for genes or open reading frame (ORF) products with the pattern in primary structures. We found that an ORF, slr0197, has the pattern in duplicate at the C-terminal region. We also found that the ORF product has a hydrophobic segment at the N-terminal region, which is followed by two internal repeats of the endonuclease domain. Based on these observations, we propose a model for the initial stage of genetic transformation. This is apparently the first report on molecular mechanisms of natural transformation.

    DOI PubMed CiNii

  • Kaneko, S., Kuno, A., Fujimoto, Z., Shimizu, D., Machida, S., Sato, Y., Yura, K., Go, M.,Mizuno, H., Taira, K., Kusakabe, I. and Hayashi, K.: An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivac・・・

    <i>FEBS letters</i>   ( 460 ) 61 - 66  1999

     View Summary

    Kaneko, S., Kuno, A., Fujimoto, Z., Shimizu, D., Machida, S., Sato, Y., Yura, K., Go, M.,Mizuno, H., Taira, K., Kusakabe, I. and Hayashi, K.: An investigation of the nature and function of module 10 in a family F/10 xylanase FXYN of Streptomyces olivaceoviridis E-86 by module shuffling with the Cex of Cellulomonas fimi and by site-directed mutagenesis.<br />

    DOI

  • Module-intron correlation and intron sliding in family F/10 xylanase genes

    Sato, Y., Niimura, Y., Yura, K., Go, M.

    Gene   238 ( 1 ) 93 - 101  1999

     View Summary

    Xylanases are classified into two families, numbered F/10 and G/11 according to the similarity of amino acid sequences of their catalytic domain (Henrissat, B., Bairoch, A., 1993. New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem. J. 293, 781-788). Three-dimensional structure of the catalytic domain of the family F/10 xylanase was reported (White, A., Withers, S.G., Gilkes, N.R., Rose, D.R., 1994. Crystal structure of the catalytic domain of the beta-1,4-glycanase Cex from Cellulomonas fimi. Biochemistry 33, 12546-12552). The domain was decomposed into 22 modules by centripetal profiles (Gb, M., Nosaka, M., 1987. Protein architecture and the origin of introns. Cold Spring Harbor Symp. Quant. Biol. 52, 915-924; Noguti, T., Sakakibara, H., Gb, M., 1993. Localization of hydrogen-bonds within modules in barnase. Proteins 16, 357-363). A module is a contiguous polypeptide segment of amino acid residues having a compact conformation within a globular domain. Collected 31 intron sites of the family F/10 xylanase genes from fungus were found to be correlated to module boundaries with considerable statistical force (p values &lt;0.001). The relationship between the intron locations and protein structures provides supporting evidence for the ancient origin of introns, because such a relationship cannot be expected by random insertion of introns into eukaryotic genes, but it rather suggests pre-existence of introns in the ancestral genes of prokaryotes and eukaryotes. A phylogenetic tree of the fungal and bacterial xylanase sequences made two clusters; one includes both the bacterial and fungal genes, but the other consists of only fungal genes. The mixed cluster of bacterial genes without introns and the fungal genes with introns further supports the ancient origin of introns. Comparison of the conserved base sequences of introns indicates that sliding of a splice site occurred in Aspergillus kawachii gene by one base from the ancestral position. Substrate-binding sites of xylanase are localized on eight modules, and introns are found at both termini of six out of these functional modules. This result suggests that introns might play a functional role in shuffling the exons encoding the substrate-binding modules. (C) 1999 Elsevier Science B.V. All rights reserved.

    DOI

  • Go, M. and Yura, K.: Protein Folding and Genome Evolution in "Old and New Views of Protein Folding(eds. Kuwajima, K. and Arai, M.)

    Elsevier     239 - 248  1999

  • Putative mechanism of natoral transformation as deduced from genome date (共著)

    DNA Research   6 ( 2 ) 75 - 82  1999

    DOI PubMed CiNii

  • Repetitive use of a phosphate-binding module in DNA polymerase β, Oct-1 POU domain and phage repressors

    Yura, K., Shionyu, M., Kawatani, K., Go, M.

    Cellular and Molecular Life Sciences   55 ( 3 ) 472 - 486  1999

     View Summary

    Motifs for sequence specific-protein-DNA interactions, such as helix-turn-helix, zinc finger and leucine zipper, are now better understood as a result of extensive studies of three-dimensional (3D) structures of transcription factors. On the other hand, little attention has been paid to motifs for sequence nonspecific binding, namely DNA-phosphate binding. To address the question whether different transcription factors and DNA manipulation enzymes, that is enzymes that work on DNA, share a similar mode of phosphate binding, we sun eyed interactions between DNA and protein module, a structural unit of a globular protein. We analyzed the modular organization of DNA polymerase beta and found that residues making contact with DNA phosphates were localized to five modules. Structural comparison of these phosphate-binding modules against others in transcription factors and DNA manipulation enzymes revealed that DNA polymerase beta. the oct-1 POU domain, 434 Cro and the Are repressor have a phosphate-binding module with 3D structures similar to one another, This newly detected module, the phosphate-binding helix-turn-helix (pbHTH) module, named for its function and 3D structure, interacts with DNA by (i) making hydrogen bonds between a DNA phosphodiester oxygen and an amino hydrogen of the main chain located at the N-terminus of a C-terminal alpha-helix. and (ii) making electrostatic interactions between DNA phosphates and side chains of lysine or arginine. Finding structurally and functionally similar phosphate-binding units in different transcription factors and DNA manipulation enzymes suggests that shuffling of modules is not limited to the DNA base-recognition motif. Phosphate-binding modules are apparently also shuffled in DNA-binding proteins.

    DOI PubMed CiNii

  • Correlation of module boundaries and intron positions in four eukaryotic transcription factors

    YURA Kei, SHIONYU Masafumi, HASHIMOTO Hiroyuki, GO Mitiko

      21   280 - 280  1998.12

    CiNii

  • Prediction of functional site based on module classification : DNA-binding mode of RNA polymerase αCTD

    YURA Kei, GO Mitiko

      21   281 - 281  1998.12

    CiNii

  • Shuffling of Xylanase Genes of Streptomyces olivaceoviridis and Thermomonospora alba and Characterization of the Translated Chimeric Enzymes

    MOHAMMAD Mainul ahsan, KANEKO Satoshi, ANISUR Rahman khan, WANG Qin, KUSAKABE Isao, SATO Yoko, YURA Kei, GO Mitiko, HAYASHI Kiyoshi

      21   326 - 326  1998.12

    CiNii

  • Construction of chimera xylanase by module substitution and the elucidation of structure-function relationship.

    金子哲, 久野敦, 清水大輔, 佐藤陽子, 由良敬, 郷通子, 日下部功, 多比良和誠, 林清

    日本農芸化学会関東支部受賞記念講演およびシンポジウム講演要旨集   1998 ( Oct ) 9  1998.10

    J-GLOBAL

  • Prediction of DNA interaction mode of RNA polymerase alpha subunit.

    Yura K., Go M.

    Biophysics   38 ( 2 ) S94  1998.09

    CiNii

  • Module Taxonomy and Its Implication to Protein Evolution

    Go M., Yura K.

    Biophysics   38 ( 2 ) S97  1998.09

    CiNii

  • Prediction of DNA interaction sites in nucleic-acid-binding proteins based on phosphate-binding helix-turn-helix module.

    Yura K., Go M.

    Biophysics   38 ( 2 ) S166  1998.09

    CiNii

  • 郷 通子、由良 敬: 相互作用と構造ブロック.「遺伝子の構造生物学」〈嶋本伸雄、郷 通子 編集)

    共立出版     169 - 179  1998

  • A new module organization of hemoglobin

    SHIONYU M., FUKAMI-KOBAYASHI K., MIZUTANI M., YURA K., GO M.

    Biophysics   37 ( 2 ) S59  1997.09

    CiNii

  • Shuffling of phosphate-binding modules in nucleic-acid-binding proteins

    YURA K., GO M.

    Biophysics   37 ( 2 ) S61  1997.09

    CiNii

  • Reconstruction of hemoglobin subunit based on new module organization

    YURA K., SHIONYU M., GO M.

    Biophysics   37 ( 2 ) S75  1997.09

    CiNii

  • Base-recognition modules and phosphate-binding modules in transcription factors

    YURA K., SHIONYU M., GO M.

    Biophysics   37 ( 2 ) S162  1997.09

    CiNii

  • Yura, K. and Go, M.: The homeodomain-like putative product of plastid genome: A possible role in plastid differentiation.

    <i>Res. Comm. Biochem. Cell & Mol. Biol.</i>   ( 1 ) 79 - 81  1997

  • 由良 敬、篠田和紀、井本剛史、郷 通子: DNA塩基配列を用いたfastDNAmlによる進化系統樹の推定

    由良 敬, 篠田 和紀, 井本 剛史, 郷 通子

    名古屋大学大型計算機センターニュース   28 ( 28 ) 127 - 135  1997

    CiNii

  • Yura, K. and Go, M.: The homeodomain-like putative product of plastid genome: A possible role in plastid differentiation.

    <i>Res. Comm. Biochem. Cell & Mol. Biol.</i>   ( 1 ) 79 - 81  1997

  • The homeodomain-like putative product of plastid genome : A possible role in plastid differentiation(共著)

    Research Communication of Biochemistry, Cell and Molecular Biology   1 ( 1 ) 79  1997

  • DNA phosphate-binding module: A new building unit for DNA-binding protein

    K Yura, K Kawatani, M Go

    PROTEIN ENGINEERING   9 ( 9 ) 9 - 9  1996.09

    Research paper, summary (international conference)  

  • トリオースリン酸イソメラーゼのモジュール境界とイントロン位置の相関

    灘浪 和彦, 由良 敬, 本多 光雄, 野口 俊之, 郷 通子

    日本分子生物学会年会プログラム・講演要旨集   19   737 - 737  1996.08

    CiNii

  • 3種のDNA結合タンパク質に共通なリン酸基結合モジュール

    由良 敬, 川谷 克司, 郷 通子

    日本分子生物学会年会プログラム・講演要旨集   19   737 - 737  1996.08

    CiNii

  • A newly identified phosphate-binding module in DNA-binding proteins

    K Yura, K Kawatani, M Go

    PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY   65   PA205 - PA205  1996

    Research paper, summary (international conference)  

  • Statistical evidence of intron-module correlation in glycolytic enzymes and origin of introns

    M Go, T Noguti, K Yura

    PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY   65   PA206 - PA206  1996

    Research paper, summary (international conference)  

  • Molecular recognition mechanism of tRNA(Glu) by glutamyl-tRNA synthetase: A study using molecular dynamics simulation and computer modeling

    M Tateno, O Nureki, K Yura, K Morikawa, T Noguti, S Yokoyama, M Go

    PROTEIN ENGINEERING   8 ( 9 ) 47 - 47  1995.09

    Research paper, summary (international conference)  

  • Tateno, M., Mizutai, M., Yura K., Nureki, O., Yokoyama, S., Go, M. Modules Structure and Function of Glutamyl-tRNA Synthetase. in "Tracing Biological Evolution in Protein and Gene Structures"(eds. M.Go and P. Schimmel)

    Elsevier     53 - 64  1995

  • Yura, K. and Go, M.: Helix-turn-helix module distribution and module shuffing. in "Tracing Biological Evolution in Protein and Gene Structures"(eds. M. Go and P. Schimmel)

    Elsevier     187 - 196  1995

  • Tateno, M., Mizutai, M., Yura K., Nureki, O., Yokoyama, S., Go, M. Modules Structure and Function of Glutamyl-tRNA Synthetase. in "Tracing Biological Evolution in Protein and Gene Structures"(eds. M.Go and P. Schimmel)

    Elsevier     53 - 64  1995

  • Yura, K. and Go, M.: Helix-turn-helix module distribution and module shuffing. in "Tracing Biological Evolution in Protein and Gene Structures"(eds. M. Go and P. Schimmel)

    Elsevier     187 - 196  1995

  • STRUCTURE OF THE HUMAN CCGI GENE - RELATIONSHIP BETWEEN THE EXONS/INTRONS AND FUNCTIONAL DOMAIN/MODULES OF THE PROTEIN (VOL 141, PG 193, 1994)

    T NAKASHIMA, T SEKIGUCHI, H SUNAMOTO, K YURA, S TOMODA, M GO, J KERE, D SCHLESSINGER, T NISHIMOTO

    GENE   148 ( 2 ) 375 - 375  1994.10

    Other  

  • STRUCTURE OF THE HUMAN CCG1 GENE - RELATIONSHIP BETWEEN THE EXONS INTRONS AND FUNCTIONAL DOMAIN MODULES OF THE PROTEIN

    T NAKASHIMA, T SEKIGUCHI, H SUNAMOTO, K YURA, S TOMODA, M GO, J KERE, D SCHLESSINGER, T NISHIMOTO

    GENE   141 ( 2 ) 193 - 200  1994.04

     View Summary

    The human CCG1 gene, encoding CCG1/TAF(II)250/p250, was isolated by complementing tsBN462, a mutant BHK21 cell line that shows cell-cycle arrest at high temperature. Using the cDNA as a probe, the locations of exon-intron junctions were determined in the genomic DNA: Thirty-eight exons ranging from 68 to 219 bp in size were found. All the exon-intron junctions followed the GT-AG rule. Using a newly developed method, we performed a module analysis of the CCG1 protein. The functional domain previously predicted in CCG1 was further confirmed to be encoded in a single predicted module that is the minimal functional unit in the protein. The boundaries of the predicted modules show a close correlation to the intron/exon junction of CCG1. The entire gene, at least 110 kb long has been recovered in a YAC, which provides a route to the further study of module function.

  • STRUCTURE OF THE HUMAN CCG1 GENE - RELATIONSHIP BETWEEN THE EXONS INTRONS AND FUNCTIONAL DOMAIN MODULES OF THE PROTEIN

    T NAKASHIMA, T SEKIGUCHI, H SUNAMOTO, K YURA, S TOMODA, M GO, J KERE, D SCHLESSINGER, T NISHIMOTO

    GENE   141 ( 2 ) 193 - 200  1994.04

     View Summary

    The human CCG1 gene, encoding CCG1/TAF(II)250/p250, was isolated by complementing tsBN462, a mutant BHK21 cell line that shows cell-cycle arrest at high temperature. Using the cDNA as a probe, the locations of exon-intron junctions were determined in the genomic DNA: Thirty-eight exons ranging from 68 to 219 bp in size were found. All the exon-intron junctions followed the GT-AG rule. Using a newly developed method, we performed a module analysis of the CCG1 protein. The functional domain previously predicted in CCG1 was further confirmed to be encoded in a single predicted module that is the minimal functional unit in the protein. The boundaries of the predicted modules show a close correlation to the intron/exon junction of CCG1. The entire gene, at least 110 kb long has been recovered in a YAC, which provides a route to the further study of module function.

  • Structure of the human CCG1 gene: relationship between the exons/introns and functional domain/modules of the protein

    Torahiko, N., Takeshi, S., Hidetoshi, S., Kei, Y., Shirou, T., Mitiko, G., Juha, K., David, S., Takeharu, N.

    Gene   141 ( 2 ) 193 - 200  1994

     View Summary

    The human CCG1 gene, encoding CCG1/TAF(II)250/p250, was isolated by complementing tsBN462, a mutant BHK21 cell line that shows cell-cycle arrest at high temperature. Using the cDNA as a probe, the locations of exon-intron junctions were determined in the genomic DNA: Thirty-eight exons ranging from 68 to 219 bp in size were found. All the exon-intron junctions followed the GT-AG rule. Using a newly developed method, we performed a module analysis of the CCG1 protein. The functional domain previously predicted in CCG1 was further confirmed to be encoded in a single predicted module that is the minimal functional unit in the protein. The boundaries of the predicted modules show a close correlation to the intron/exon junction of CCG1. The entire gene, at least 110 kb long has been recovered in a YAC, which provides a route to the further study of module function.

    DOI PubMed CiNii

  • ESSENTIAL ROLE OF THE ARG112 RESIDUE OF CYTOCHROME-P450CAM FOR ELECTRON-TRANSFER FROM REDUCED PUTIDAREDOXIN

    H KOGA, Y SAGARA, T YAOI, M TSUJIMURA, K NAKAMURA, K SEKIMIZU, R MAKINO, H SHIMADA, Y ISHIMURA, K YURA, M GO, M IKEGUCHI, T HORIUCHI

    FEBS LETTERS   331 ( 1-2 ) 109 - 113  1993.09

     View Summary

    Cytochrome P450 cam (CYP101) of Pseudomonas putida PpG1 in which Arg112 is substituted by Cys was isolated by in vitro random mutagenesis of the camC gene DNA coding for P450cam. The absorption spectra of the purified mutant enzyme were similar to those of the wild type enzyme, but its substrate-dependent NADH oxidation activity in the presence of putidaredoxin (Pd) and putidaredoxin reductase (PdR) was extremely low. The rate constant of electron transfer from reduced Pd to the heme of the mutant P450cam, measured on an anaerobic stopped flow apparatus, was 1/400 of that of the wild type enzyme and the dissociation constant of the mutant P450cam for oxidized Pd was several fold higher than that of the wild type enzyme. A considerable decrease in mid-point potential of the mutant enzyme was also noted. We conclude that Arg112, which is located on the surface of the P450cam molecule and hydrogen-bonded to one of the heme propionate chains, plays an essential role in the electron transfer from Pd.

    DOI

  • ESSENTIAL ROLE OF THE ARG112 RESIDUE OF CYTOCHROME-P450CAM FOR ELECTRON-TRANSFER FROM REDUCED PUTIDAREDOXIN

    H KOGA, Y SAGARA, T YAOI, M TSUJIMURA, K NAKAMURA, K SEKIMIZU, R MAKINO, H SHIMADA, Y ISHIMURA, K YURA, M GO, M IKEGUCHI, T HORIUCHI

    FEBS LETTERS   331 ( 1-2 ) 109 - 113  1993.09

     View Summary

    Cytochrome P450 cam (CYP101) of Pseudomonas putida PpG1 in which Arg112 is substituted by Cys was isolated by in vitro random mutagenesis of the camC gene DNA coding for P450cam. The absorption spectra of the purified mutant enzyme were similar to those of the wild type enzyme, but its substrate-dependent NADH oxidation activity in the presence of putidaredoxin (Pd) and putidaredoxin reductase (PdR) was extremely low. The rate constant of electron transfer from reduced Pd to the heme of the mutant P450cam, measured on an anaerobic stopped flow apparatus, was 1/400 of that of the wild type enzyme and the dissociation constant of the mutant P450cam for oxidized Pd was several fold higher than that of the wild type enzyme. A considerable decrease in mid-point potential of the mutant enzyme was also noted. We conclude that Arg112, which is located on the surface of the P450cam molecule and hydrogen-bonded to one of the heme propionate chains, plays an essential role in the electron transfer from Pd.

    DOI PubMed CiNii

  • REPEAT OF A HELIX-TURN-HELIX MODULE IN DNA-BINDING PROTEINS

    K YURA, S TOMODA, M GO

    PROTEIN ENGINEERING   6 ( 6 ) 621 - 628  1993.08

    Authorship:Lead author

     View Summary

    Helix-turn-helix motif is one of the common motifs observed in DNA-binding proteins. The motif interacts with DNA double helix and recognizes specific base sequences. It is assumed that the helix - turn - helix motif appears only once in seven prokaryotic transcriptional repressors of which 3-D structures have been determined by X-ray crystallographic studies. These prokaryotic repressors consist of several alpha-helices connected with turns. We report here that these repressors are decomposable into helix - turn - helix modules and their connectors. A module is defined as a compact structural unit with consecutive amino acid residues in a globular protein. Each of the helix - turn - helix motifs in the seven proteins corresponds approximately to a single helix-turn-helix module consisting of approximately 13 amino acids. Identification of modules of seven prokaryotic repressors and comparisons of their tertiary structures led to the conclusion that three of these DNA-binding proteins contain more than one helix - turn - helix module with a structure similar to the helix-turn-helix motif. The difference in module organization of these DNA-binding proteins paves the way for further classification of the DNA-binding proteins with the helix-turn-helix motif. The structural repertoire of these transcriptional regulators was increased through different utilizations in the number of helix - turn - helix and other modules. The difference in DNA base recognition ability in these helix - turn - helix modules is ascribed to a difference in size of a side chain at the fifth residue from Gly, on the turn.

  • REPEAT OF A HELIX-TURN-HELIX MODULE IN DNA-BINDING PROTEINS

    K YURA, S TOMODA, M GO

    PROTEIN ENGINEERING   6 ( 6 ) 621 - 628  1993.08

     View Summary

    Helix-turn-helix motif is one of the common motifs observed in DNA-binding proteins. The motif interacts with DNA double helix and recognizes specific base sequences. It is assumed that the helix - turn - helix motif appears only once in seven prokaryotic transcriptional repressors of which 3-D structures have been determined by X-ray crystallographic studies. These prokaryotic repressors consist of several alpha-helices connected with turns. We report here that these repressors are decomposable into helix - turn - helix modules and their connectors. A module is defined as a compact structural unit with consecutive amino acid residues in a globular protein. Each of the helix - turn - helix motifs in the seven proteins corresponds approximately to a single helix-turn-helix module consisting of approximately 13 amino acids. Identification of modules of seven prokaryotic repressors and comparisons of their tertiary structures led to the conclusion that three of these DNA-binding proteins contain more than one helix - turn - helix module with a structure similar to the helix-turn-helix motif. The difference in module organization of these DNA-binding proteins paves the way for further classification of the DNA-binding proteins with the helix-turn-helix motif. The structural repertoire of these transcriptional regulators was increased through different utilizations in the number of helix - turn - helix and other modules. The difference in DNA base recognition ability in these helix - turn - helix modules is ascribed to a difference in size of a side chain at the fifth residue from Gly, on the turn.

  • REPEAT OF A HELIX-TURN-HELIX MODULE IN DNA-BINDING PROTEINS

    K YURA, S TOMODA, M GO

    PROTEIN ENGINEERING   6 ( 6 ) 621 - 628  1993.08

     View Summary

    Helix-turn-helix motif is one of the common motifs observed in DNA-binding proteins. The motif interacts with DNA double helix and recognizes specific base sequences. It is assumed that the helix - turn - helix motif appears only once in seven prokaryotic transcriptional repressors of which 3-D structures have been determined by X-ray crystallographic studies. These prokaryotic repressors consist of several alpha-helices connected with turns. We report here that these repressors are decomposable into helix - turn - helix modules and their connectors. A module is defined as a compact structural unit with consecutive amino acid residues in a globular protein. Each of the helix - turn - helix motifs in the seven proteins corresponds approximately to a single helix-turn-helix module consisting of approximately 13 amino acids. Identification of modules of seven prokaryotic repressors and comparisons of their tertiary structures led to the conclusion that three of these DNA-binding proteins contain more than one helix - turn - helix module with a structure similar to the helix-turn-helix motif. The difference in module organization of these DNA-binding proteins paves the way for further classification of the DNA-binding proteins with the helix-turn-helix motif. The structural repertoire of these transcriptional regulators was increased through different utilizations in the number of helix - turn - helix and other modules. The difference in DNA base recognition ability in these helix - turn - helix modules is ascribed to a difference in size of a side chain at the fifth residue from Gly, on the turn.

  • Essential role of the Arg112 residue of cytochrome P450cam for electron transfer from reduced putidaredoxin

    Koga, H., Sagara, Y., Yaoi, T., Tsujimura, M., Nakamura, K., Sekimizu, K., Makino, R., Shimada, H., Ishimura, Y., Yura, K., Go, M., Ikeguchi, M., Horiuchi, T.

    FEBS Letters   331 ( 1-2 ) 109 - 113  1993

     View Summary

    Cytochrome P450 cam (CYP101) of Pseudomonas putida PpG1 in which Arg112 is substituted by Cys was isolated by in vitro random mutagenesis of the camC gene DNA coding for P450cam. The absorption spectra of the purified mutant enzyme were similar to those of the wild type enzyme, but its substrate-dependent NADH oxidation activity in the presence of putidaredoxin (Pd) and putidaredoxin reductase (PdR) was extremely low. The rate constant of electron transfer from reduced Pd to the heme of the mutant P450cam, measured on an anaerobic stopped flow apparatus, was 1/400 of that of the wild type enzyme and the dissociation constant of the mutant P450cam for oxidized Pd was several fold higher than that of the wild type enzyme. A considerable decrease in mid-point potential of the mutant enzyme was also noted. We conclude that Arg112, which is located on the surface of the P450cam molecule and hydrogen-bonded to one of the heme propionate chains, plays an essential role in the electron transfer from Pd.

    DOI

  • Saito, N., Yura, K. and Fukuda, Y.:Some remarks on protein folding. in "Protein Structural Analysis, Folding and Design" (ed. M. Hatano)

    Japan Sci. soc. Press and Elsevier     19  1990

  • Saito, N., Yura, K. and Fukuda, Y.:Some remarks on protein folding. in "Protein Structural Analysis, Folding and Design" (ed. M. Hatano)

    Japan Sci. soc. Press and Elsevier     19  1990

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Syllabus

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Social Activities

  • International Biophysical Congress 2024 (Kyoto)

    (京都) 

    2024.06
    -
     

  • 産業経済新聞

    2021.12
    -
     

     View Summary

    コオロギ食が世界を救う

Academic Activities

  • 日本生物物理学会

    2011.01
    -
    2012.12
  • 日本生物物理学会

    2005.01
    -
    2008.12
  • World Wide Protein Data Bank (wwPDB)

    2005.01
    -
    2008.12

Sub-affiliation

  • Affiliated organization   Global Education Center

  • Faculty of Science and Engineering   Graduate School of Advanced Science and Engineering

Research Institute

  • 2022
    -
    2024

    Waseda Research Institute for Science and Engineering   Concurrent Researcher

Internal Special Research Projects

  • 創薬等のプロジェクトを支援するヒトゲノムアノテーションデータベースの開発

    2018   鈴木博文

     View Summary

    薬物などの低分子を細胞外に排出するATP-binding cassette (ABC)輸送体は、ヒトゲノムに48種類存在する。これらの遺伝子の一塩基置換が多数報告されており、疾患の原因になる場合も知られている。しかし、疾患につながる置換とつながらない置換に、明確な違いが見いだせていない。ABC輸送体の立体構造データと変異データとをつないだところ、疾患につながる変異は、ABC輸送体の機能的構造変化の要となる部分に存在する場合があることがわかった。これら以外の部位に存在する変異が、どのような機構で疾患につながるかは未知だが、今回のデータ連結によって疾患につながる一つの機構を見いだすことができた。

  • オミックスデータ融合による細胞内生体高分子の時空間構造再構築

    2018  

     View Summary

    肺炎レンサ球菌は、呼吸器系感染症などの原因バクテリアであり、その増殖を抑える低分子が開発されている。SCNはその一つであるが、SCNが低濃度の場合は効き目がない。SCNが低濃度投与された際に、各遺伝子がどのように発現するのかを調べたビッグデータを取得し、オミックスデータの融合を試みた。その結果、SCN投与後から5分までの間に、二次代謝産物生合成系の遺伝子発現は増加していることがわかった。そして、15分後には薬剤排出の遺伝子も活発に発現することがわかった。低濃度のSCNでは、薬剤代謝に関係する遺伝子の発現を抑えきれず、むしろ薬物防御機構が活性化されていることがわかった。

  • オミックスデータの融合による生体高分子の細胞内時空間構造の再構築

    2017  

     View Summary

    オミックスデータが豊富に得られているバクテリアであるStreptococcus pneumoniaeをモデルケースとした。ゲノム塩基配列、遺伝子領域、転写因子と転写制御を受ける遺伝子の関係、およびタンパク質の相互作用解析結果が公開されている。これらのデータ全体を、ゲノム情報を軸として接続することができた。データを接続した結果、既知転写因子のみでは転写のネットワークが閉じていないことが明らかになり、つまり未知転写因子が存在することがわかった。また既知転写因子の中で、CcpAが一番多くの遺伝子制御に関わっており、またSpxが一番多くのタンパク質と相互作用することがわかった。

  • RNAはどのような三次元構造でタンパク質と相互作用するのか

    2017  

     View Summary

    当該研究では、RNAとタンパク質の複合体構造を推定する方法の開発をめざして、まずRNA構造の特徴抽出を行った。2017年8月現在の生体高分子立体構造データベース(PDB)には、RNA分子単独の立体構造が1327件、タンパク質との複合体が2002件存在することがわかった。RNA分子単独の立体構造において、鎖の順番に現れるリン原子が空間的にどのように分布するかを、10Åを閾値として自己相関を調べたところ、20塩基ごとに何らかのまとまった構造を形成していることがわかった。このことは、RNAの立体構造推定において、20塩基程度の立体構造推定を行い、そのブロックを組み合わせればよいことを示唆する。