Updated on 2022/09/28

写真a

 
YURA, Kei
 
Affiliation
Faculty of Science and Engineering, School of Advanced Science and Engineering
Job title
Professor(without tenure)

Concurrent Post

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

  • Affiliated organization   Global Education Center

Research Institute

  • 2020
    -
    2022

    理工学術院総合研究所   兼任研究員

Education

  •  
    -
    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  

Degree

  • Waseda University   (BLANK)

  • Nagoya University   (BLANK)

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

Professional Memberships

  •  
     
     

    米国生物物理学会

  •  
     
     

    日本生化学会

  •  
     
     

    日本蛋白質科学会

  •  
     
     

    日本遺伝学会

  •  
     
     

    日本分子生物学会

  •  
     
     

    日本生物物理学会

▼display all

 

Research Areas

  • System genome science

  • Life, health and medical informatics

  • Biophysics

  • Genome biology

Research Interests

  • Biophysics

  • Computational biology

Papers

  • 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

     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

  • 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  [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

  • 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    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

  • 昆虫を活用した新たな食料生産システムの構築

    由良 敬, 鈴木丈詞, 渡邉崇人, 小倉 淳, 朝日 透, 生田和正, 霜田政美, 森岡伸介, 佐藤秀一, 中村龍平

    JATAFFジャーナル   9 ( 6 ) 14 - 19  2021.06

  • 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

  • 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.

    DOI PubMed

  • 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

  • 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

  • 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

  • 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   591 - 599  2020.07  [Refereed]

    DOI

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

    Kei Yura

    Mammalian Genome    2020.07

    DOI

  • 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

  • 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

  • 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

  • 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

  • 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

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

    Kei Yura

    Photochemistry and Photobiology    2019.09

    DOI

  • 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

  • Relationship between conformation shift and disease related variation sites in ATP-binding cassette transporter proteins

    Kei Yura

    Biophysics and Physicobiology   16 ( 0 ) 68 - 79  2019  [Refereed]

    DOI

  • 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

  • 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

  • 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

  • Preface of Special Issue "Databases".

    Yura K

    Biophysics and physicobiology   15   86  2018  [Refereed]

    DOI PubMed

  • 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

  • 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

  • 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

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

    Yura K

    Biophysics and physicobiology   13   85 - 86  2016  [Refereed]

    DOI PubMed CiNii

  • 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

  • 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

  • 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

  • Memorial Issue for Professor Nobuhiko Saitô.

    Yura K, Wako H

    Biophysics and physicobiology   13   243 - 243  2016  [Refereed]

    DOI PubMed CiNii

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • [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

  • 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

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

    YURA Kei

    Seibutsu Butsuri   52 ( 6 ) 304 - 305  2012.11

    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

  • 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

  • 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

  • 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

  • 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

  • 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.

    DOI PubMed

  • 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

  • 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.

    DOI PubMed

  • 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.

    DOI PubMed

  • 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

  • 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

  • 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.

    DOI PubMed

  • 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

  • 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

  • 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.

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

▼display all

Books and Other Publications

  • 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

Misc

  • タイワンエンマコオロギのゲノム全塩基配列解読:大量生産に向けた高効率品種改良技術の幕開け

    片岡孝介, 嶺井隆平, 井手圭吾, 井手圭吾, 小倉淳, 竹山春子, 竹山春子, 竹田真木生, 鈴木丈詞, 由良敬, 由良敬, 由良敬, 朝日透

    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

  • 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   2301  2005

  • 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 )  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

  • RNAポリメラーゼαサブユニットのDNA結合様式の推定

    由良 敬, 郷 通子

    生物物理   38 ( 2 )  1998.09

    CiNii

  • モジュールの博物学的整理

    郷 通子, 由良 敬

    生物物理   38 ( 2 )  1998.09

    CiNii

  • リン酸基結合ヘリックス・ターン・ヘリックスモジュールを用いた核酸-蛋白質相互作用部位の推定

    由良 敬, 郷 通子

    生物物理   38 ( 2 )  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

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

  • 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

▼display all

Research Projects

  • 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。

  • 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

  • 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
    -
     
     

  • 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

Specific Research

  • 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。

  • 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。

  • 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。

 

Syllabus

▼display all

 

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