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Exploration of the conformational spaces of oligosaccharides based on NMR analyses and deciphering the dynamic glycocode

Research Project

Project/Area Number 15K17889
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionJapan Advanced Institute of Science and Technology

Principal Investigator

Yamaguchi Takumi  北陸先端科学技術大学院大学, 先端科学技術研究科, 准教授 (60522430)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖鎖 / NMR / 分子シミュレーション / ダイナミクス / 立体構造解析
Outline of Final Research Achievements

Oligosaccharides play pivotal roles in a variety of biological events in intracellular environments primarily through their interactions with a series of carbohydrate recognition proteins. In this study, the dynamic conformational ensemble of the high-mannose-type dodecasaccharide that displays the terminal glucose residue as a determinant recognized by molecular chaperones was determined. For this purpose, we attempted to apply the method based on paramagnetism-assisted NMR spectroscopy in conjunction with molecular dynamics simulation. A key to exploiting this method is the preparation of sufficient quantities of the lanthanide-tagged oligosaccharide with uniform and selective stable isotope-labelling. This was enabled by using a chemoenzymatic technique that we also developed. Consequently, our exploration of the conformational space of this dodecasaccharide revealed an induced-fit mechanism by which the chaperone accommodates the glucosyl antenna of their targets.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 7 results,  Invited: 7 results) Book (4 results)

  • [Journal Article] Conformational analysis of a high-mannose-type oligosaccharide displaying glucosyl determinant recognised by molecular chaperones using NMR-validated molecular dynamics simulation2017

    • Author(s)
      T.Suzuki, M.Kajino, S.Yanaka, T.Zhu, H.Yagi, T.Satoh, T.Yamaguchi, and K.Kato
    • Journal Title

      ChemBioChem

      Volume: 18 Issue: 4 Pages: 396-410

    • DOI

      10.1002/cbic.201600595

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hyper-assembly of Self-assembled Glycoclusters Mediated by Specific Carbohydrate-carbohydrate Interactions2017

    • Author(s)
      Yan, G.; Yamaguchi, T.; Suzuki, T.; Yanaka, S.; Sato, S.;Fujita, M.; Kato, K.
    • Journal Title

      Chem. Asian J.

      Volume: 12 Issue: 9 Pages: 968-972

    • DOI

      10.1002/asia.201700202

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control2016

    • Author(s)
      T. Satoh, T. Toshimori, G. Yan, T. Yamaguchi, K. Kato
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 20575-20575

    • DOI

      10.1038/srep20575

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A hybrid strategy for the preparation of 13C-labeled high-mannose-type oligosaccharides with terminal glucosylation for NMR study2015

    • Author(s)
      T. Zhu, T. Yamaguchi, T. Satoh and K. Kato
    • Journal Title

      Chem. Lett.

      Volume: 44 Issue: 12 Pages: 1744-1746

    • DOI

      10.1246/cl.150898

    • NAID

      130005112523

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 糖鎖の生命分子科学の新展開2015

    • Author(s)
      山口拓実, 矢木真穂, 加藤晃一
    • Journal Title

      機器センターたより

      Volume: 7 Pages: 74-78

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paramagnetic NMR probes for characterization of the dynamic conformations and interactions of oligosaccharides2015

    • Author(s)
      K. Kato, T. Yamaguchi
    • Journal Title

      Glycoconjugate J.

      Volume: 32 Issue: 7 Pages: 505-513

    • DOI

      10.1007/s10719-015-9599-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 糖鎖のNMR相互作用解析のための常磁性プローブの合成2017

    • Author(s)
      堀 由樹、Yan Gengwei、山口拓実
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] NMR analyses of the dynamic structure and interactions of Lewis X oligosaccharide and its cluster2017

    • Author(s)
      Gengwei Yan, Tatsuya Suzuki, Saeko Yanaka, Takumi Yamaguchi, Makoto Fujita, Koichi Kato
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 分子シミュレーションを用いたルイスX糖鎖の構造揺らぎ探査2017

    • Author(s)
      村上真吾、Yan Gengwei、山口拓実
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      慶應義塾大学(神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synthesis and modifications of oligosaccharides toward understanding their functioning mechanisms2017

    • Author(s)
      Takumi Yamaguchi
    • Organizer
      JAIST Japan-India Symposium on Materials Science 2017
    • Place of Presentation
      北陸先端科学技術大学院大学(石川県能美市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 磁性金属プローブを活用した生体分子の構造解析2016

    • Author(s)
      山口拓実
    • Organizer
      平成28年度 錯体化学若手の会・北陸支部勉強会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Biophysical and chemical approaches to dynamic conformations of oligosaccharides2016

    • Author(s)
      Takumi Yamaguchi
    • Organizer
      CARBO- XXXI International Conference on "New Frontiers in Carbohydrate Chemistry and Biology”
    • Place of Presentation
      Delhi, India
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Creation of self-assembled glycoclusters for characterizing sugar-sugar interactions2016

    • Author(s)
      Gengwei Yan, Takumi Yamaguchi, Saeko Yanaka, Tatsuya Suzuki, Makoto Fujita, Koichi Kato
    • Organizer
      2nd International Symposium on Center of Excellence for Innovative Material Sciences Based on Supramolecule
    • Place of Presentation
      石川県文教会館(石川県金沢市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖鎖の分子科学:化学・生物学・物理学を横断して2016

    • Author(s)
      山口拓実
    • Organizer
      第3回「動的秩序と機能」若手研究会
    • Place of Presentation
      加賀観光ホテル(石川県加賀市)
    • Year and Date
      2016-10-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 安定同位体標識モノグルコシル化糖鎖の調製とNMR立体構造解析2016

    • Author(s)
      山口拓実,Zhu Tong,佐藤匡史,加藤晃一
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      同志社大学京田辺キャンパス(京都府京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] NMRと分子シミュレーションによる糖鎖の三次元構造ダイナミクスの描像2016

    • Author(s)
      山口拓実
    • Organizer
      蛋白研セミナー「構造を基盤とする蛋白質科学における未解決問題」
    • Place of Presentation
      東京大学先端科学技術研究センター(東京都目黒区)
    • Year and Date
      2016-03-02
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Chemical synthesis and modification of oligosaccharides toward controlling their biofunctions2016

    • Author(s)
      Takumi Yamaguchi
    • Organizer
      DU-JAIST Indo-Japan Symposium on Chemistry of Functional Molecules/ Materials
    • Place of Presentation
      New Delhi, India
    • Year and Date
      2016-02-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Conformational dynamics of high-mannose-type oligosaccharides as studied by NMR spectroscopy combined with molecular dynamics simulation2015

    • Author(s)
      Takumi Yamaguchi, Tadashi Satoh, Tong Zhu, and Koichi Kato
    • Organizer
      The 2015 International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2015)
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2015-12-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural basis of the molecular mechanisms underlying intracellular quality control of glycoproteins mediated by the ER folding sensor enzyme UGGT2015

    • Author(s)
      Tong Zhu, 山口拓実, 佐藤匡史, 加藤晃一
    • Organizer
      糖鎖科学中部拠点第12回「若手の力」フォーラム
    • Place of Presentation
      名城大学薬学部ライフサイエンスホール(愛知県名古屋市)
    • Year and Date
      2015-11-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Structural insights into intracellular quality control of glycoproteins mediated by their glucosylation2015

    • Author(s)
      Tong Zhu, Tadashi Satoh, Takumi Yamaguchi, and Koichi Kato
    • Organizer
      The 4th International Symposium on Dynamical Ordering of Biomolecular Systems
    • Place of Presentation
      九州大学西新プラザ(福岡県福岡市)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 分岐鎖糖鎖の配座空間探査における常磁性効果の活用2015

    • Author(s)
      山口拓実,Tong Zhu,佐藤匡史,加藤晃一
    • Organizer
      第54回 NMR討論会
    • Place of Presentation
      千葉工業大学津田沼キャンパス(千葉県習志野市)
    • Year and Date
      2015-11-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Paramagnetic Lanthanide-tagging for NMR Characterization of The Conformational Dynamics of Oligosaccharides2015

    • Author(s)
      Takumi Yamaguchi and Koichi Kato
    • Organizer
      IMS Asian International Symposium "Supramolecular Dynamics at the Interface of Chemistry and Biology"
    • Place of Presentation
      岡崎コンファレンスセンター(愛知県岡崎市)
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] NMR in Glycoscience and Glycotechnology2017

    • Author(s)
      M. Yagi-Utsumi, T. Yamaguchi, Y. Uekusa, K. Kato
    • Publisher
      RSC Publishing (Cambridge)
    • Related Report
      2016 Annual Research Report
  • [Book] Modern Magnetic Resonance2017

    • Author(s)
      K. Kato, H. Yagi, T. Yamaguchi
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Molecular Science of Fluctuations Toward Biological Functions2016

    • Author(s)
      M. Yagi-Utsumi, T. Yamaguchi, R. Kitahara, K. Kato
    • Total Pages
      270
    • Publisher
      Springer (Japan)
    • Related Report
      2015 Research-status Report
  • [Book] 糖鎖の新機能開発・応用ハンドブック~創薬・医療から食品開発まで~2015

    • Author(s)
      山口拓実, 加藤晃一
    • Total Pages
      628
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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