Elucidation of the dynamic conformations and interactions of oligosaccharides by using paramagnetic NMR probes

• Project/Area Number: 24750170
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemistry related to living body
• Research Institution: Institute for Molecular Science
• Principal Investigator: YAMAGUCHI Takumi 分子科学研究所, 生命・錯体分子科学研究領域, 助教 (60522430)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 糖鎖 / NMR / 常磁性 / 立体構造解析 / ダイナミクス

Outline of Final Research Achievements

Elucidation of physicochemical basis of the biological functions of oligosaccharides remains as tasks with more challenges. Paramagnetism-assisted NMR techniques using lanthanide ion-chelating probes was combined with molecular dynamics simulations to explore the conformational spaces of oligosaccharides in solution. The experimentally validated simulation results successfully provided atomic descriptions of dynamic behaviors of oligosaccharides such as high-mannose-type oligosaccharides harboring intracellular glycoprotein-fate determinants in their branched structures. The data showed conformational selection mechanisms by the carbohydrate recognition proteins during the glycan recognition process. These results suggest that dynamic conformational rearrangements of oligosaccharides can be important factors in inspecting carbohydrate-binding affinities and specificities of the lectins and enzymes in cells.

Research Products

• [Journal Article] Emerging structural insights into glycoprotein quality control coupled with N-glycan processing in the endoplasmic reticulum (2015)
  • Author(s): T.Satoh, T.Yamaguchi, and K.Kato
  • Journal Title: Molecules Volume: 20 Issue: 2 Pages: 2475-2491
  • DOI: 10.3390/molecules20022475
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Depicting the Dynamic Conformations of Sugar Chains (2015)
  • Author(s): 山口拓実, 加藤晃一
  • Journal Title: Seibutsu Butsuri Volume: 55 Issue: 2 Pages: 081-083
  • DOI: 10.2142/biophys.55.081
  • NAID: 130005061222
  • ISSN: 0582-4052, 1347-4219
  • Peer Reviewed / Open Access
• [Journal Article] Exploration of conformational spaces of high-mannose-type oligosaccharides by an NMR-validated simulation (2014)
  • Author(s): T.Yamaguchi, Y.Sakae, Y.Zhang, S.Yamamoto, Y.Okamoto, and K.Kato
  • Journal Title: Angew. Chem. Int. Ed. Volume: 53 Issue: 41 Pages: 10941-10944
  • DOI: 10.1002/ange.201406145
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] New NMR tools for characterizing the dynamic conformations and interactions of oligosaccharides (2013)
  • Author(s): Ying Zhang, Takumi Yamaguchi, and Koichi Kato
  • Journal Title: Chem. Lett. Volume: 42 Issue: 12 Pages: 1455-1462
  • DOI: 10.1246/cl.130789
  • NAID: 130004867848
  • Peer Reviewed
• [Journal Article] Ganglioside-embedding small bicelles for probing membrane-landing processes of intrinsically disordered proteins. (2013)
  • Author(s): T.Yamaguchi, T.Uno, Y.Uekusa, M.Yagi-Utsumi, and K.Kato
  • Journal Title: Chem. Commun. Volume: 49 Issue: 12 Pages: 1235-1237
  • DOI: 10.1039/c2cc38016a
  • Peer Reviewed
• [Journal Article] Application of metabolic ^<13>C labeling in conjunction with high-field nuclear magnetic resonance spectroscopy for comparative conformational analysis of high mannose-type oligosaccharides. (2013)
  • Author(s): Y.Kamiya, K.Yanagi, T.Kitajima, T.Yamaguchi, Y.Chiba, and K.Kato
  • Journal Title: Biomolecules Volume: 3 Issue: 1 Pages: 108-123
  • DOI: 10.3390/biom3010108
  • Peer Reviewed
• [Journal Article] Terminal spin labeling of a high-mannose-type oligosaccharide for quantitative NMR analysis of its dynamic conformation (2013)
  • Author(s): Takumi Yamaguchi, Yukiko Kamiya, Yeun-Mun Choo, Sayoko Yamamoto, and Koichi Kato
  • Journal Title: Chem. Lett. Volume: 42 Pages: 544-546
  • NAID: 10031167819
  • Peer Reviewed
• [Presentation] NMR解析に基づく分子シミュレーションによる高マンノース型糖鎖の動的立体構造の解明 (2015)
  • Author(s): 山口拓実, 榮 慶丈, 岡本祐幸, 加藤晃一
  • Organizer: 日本化学会 第95春季年会
  • Place of Presentation: 日本大学理工学（千葉県船橋市）
  • Year and Date: 2015-03-27
• [Presentation] Elucidation of conformational dynamics of oligosaccharides by NMR spectroscopy and molecular dynamics simulation (2015)
  • Author(s): T. Yamaguchi, Y. Zhang, and K. Kato
  • Organizer: The 5th Yonsei-IMS Joint Workshop: “Multilateral approaches for investigating biomolecular structures and functions”
  • Place of Presentation: 箱根高原ホテル（神奈川県足柄下郡）
  • Year and Date: 2015-01-31
• [Presentation] Elucidation of the molecular basis of oligosaccharide functions by NMR spectroscopy and molecular dynamics simulation (2015)
  • Author(s): T. Yamaguchi, Y. Sakae, M. Yagi-Utsumi, Y. Zhang, S. Yamamoto, Y. Okamoto, and K. Kato
  • Organizer: The 3rd International Symposium on Dynamical Ordering of Biomolecular Systems for Creation of Integrated Functions
  • Place of Presentation: 合歓の郷（三重県志摩市）
  • Year and Date: 2015-01-10
  • Invited
• [Presentation] Exploration of conformational dynamics of oligosaccharides by stable isotope- and lanthanide- assisted NMR approaches (2014)
  • Author(s): T. Yamaguchi, Y. Zhang, Y. Kamiya, S. Yamamoto, and K. Kato
  • Organizer: XXVIth International Conference on Magnetic Resonance in Biological Systems (ICMRBS)
  • Place of Presentation: Dallas (USA)
  • Year and Date: 2014-08-28
• [Presentation] 揺らめく糖鎖のかたちとはたらき (2014)
  • Author(s): 山口拓実
  • Organizer: 宇宙・生命・脳・物質・エネルギー」若手研究者による Rising Sun Ⅲ
  • Place of Presentation: 日本科学未来館（東京都江東区）
  • Year and Date: 2014-06-15
  • Invited
• [Presentation] Paramagnetism-assisted NMR approaches to the molecular basis of oligosaccharide functions (2014)
  • Author(s): Takumi Yamaguchi, Ying Zhang, Yukiko Kamiya, Yoshitake Sakae, Yuko Okamoto, and Koichi Kato
  • Organizer: The 2nd International Symposium on Dynamical Ordering of Biomolecular Systems for Creation of Integrated Functions
  • Place of Presentation: キャンパスプラザ京都（京都府京都市）
• [Presentation] Paramagnetic NMR approaches for revealing conformational dynamics of oligosaccharides (2013)
  • Author(s): Takumi Yamaguchi, Ying Zhang, and Koichi Kato
  • Organizer: 8th Asian Biophysics Association Symposium (ABA Jeju 2013)
  • Place of Presentation: Jeju (Korea)
• [Presentation] 安定同位体標識と常磁性プローブ導入による高マンノース型糖鎖のNMR動的構造解析 (2013)
  • Author(s): 山口拓実，Zhang Ying，王 進政，喜多島敏彦，千葉靖典，戸谷希一郎，神谷由紀子，加藤晃一
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪国際交流センター（大阪府大阪市）
• [Presentation] NMRを用いた糖鎖のコンフォメーション揺らぎとクラスター特性の解析 (2013)
  • Author(s): 山口拓実，加藤晃一
  • Organizer: 国際高等研研究プロジェクト「分子基盤に基づく生体機能ネットワークとダイナミクスの解明」
  • Place of Presentation: 国際高等研究所（京都府木津川市）
  • Invited
• [Presentation] ランタニドイオンを活用した常磁性NMR法による糖鎖の動的構造解析 (2013)
  • Author(s): 山口拓実，Zhang Ying，王 進政，戸谷希一郎，榮 慶丈，岡本祐幸，神谷由紀子，加藤 晃一
  • Organizer: 第7回バイオ関連化学シンポジウム
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
• [Presentation] 常磁性効果を活用した糖鎖の立体構造解析－NMRと分子動力学計算によるコンフォメーション空間の探査－ (2013)
  • Author(s): 山口拓実
  • Organizer: 日本分光学会NMR分光部会 平成25年度講習会
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
  • Invited
• [Presentation] 生命分子アッセンブリーにおける分子間相互作用のダイナミクス精密解析 (2013)
  • Author(s): 加藤晃一，山口拓実
  • Organizer: 山田研究会・統合バイオサイエンスシンポジウム
  • Place of Presentation: 伊良湖ビューホテル（愛知県田原市）
  • Invited
• [Presentation] Paramagnetism-assisted NMR evaluation of molecular dynamics simulations for conformational characterization of oligosaccharides (2013)
  • Author(s): Takumi Yamaguchi, Ying Zhang, Yukiko Kamiya, Yoshitake Sakae, Yuko Okamoto, and Koichi Kato
  • Organizer: 6th Japan-Korea Seminars on Biomolecular Science : Experiments and Simulation
  • Place of Presentation: 岡崎コンファレンスセンター（愛知県岡崎市）
• [Presentation] 核磁気共鳴法による糖鎖の3次元構造ダイナミクスの解明 (2013)
  • Author(s): 山口拓実
  • Organizer: 第2回 NINS Colloquium
  • Place of Presentation: ヤマハリゾードつま恋（静岡県掛川市）
• [Presentation] 常磁性NMR分光法と分子動力学計算を組み合わせた糖鎖の動的立体構造解析
  • Author(s): 山口拓実，Zhang Ying，山本さよこ，加藤晃一
  • Organizer: 第39回生体分子科学討論会
  • Place of Presentation: 東北大学（宮城）
• [Presentation] NMRを用いた糖鎖の動的立体構造解析
  • Author(s): 山口拓実
  • Organizer: 分子研若手の会
  • Place of Presentation: 分子科学研究所（愛知）
  • Invited
• [Presentation] Oligosaccharide conformational dynamics analyses by using PCS in conjunction with MD simulation
  • Author(s): Ying Zhang, Takumi Yamaguchi, Sayoko Yamamoto, Koichi Kato
  • Organizer: 26 International Carbohydrate Symposium
  • Place of Presentation: Madrid (Spain)
• [Presentation] 分子動力学計算と常磁性NMR法による糖鎖の立体構造揺らぎの評価
  • Author(s): 山口拓実，Zhang Ying，山本さよこ，亀田倫史，加藤晃一
  • Organizer: 新学術領域「揺らぎと生体機能」「水和とATP」合同公開シンポジウム「ゆらぎと水－生命のエネルギーと分子機構を探る」
  • Place of Presentation: 大阪ガーデンパレス（大阪）
• [Presentation] 常磁性NMR法による糖鎖の動的立体構造解析
  • Author(s): 山口拓実，Zhang Ying，山本さよこ，亀田倫史，Erdelyi Mate，Griesinger Christian，加藤晃一
  • Organizer: 第31回 日本糖質学会年会
  • Place of Presentation: 鹿児島市民文化ホール（鹿児島）
• [Presentation] Paramagnetic-assisted NMR analyses of conformational dynamics of gangliosides
  • Author(s): Ying Zhang, Takumi Yamaguchi, Sayoko Yamamoto, Yoshinori Uekusa and Koichi Kato
  • Organizer: 4th Asian Communications of Glycobiology and Glycotechnology (ACGG 2012 Conference)
  • Place of Presentation: Jeju (Korea)
• [Presentation] Comparative conformational analysis of high-mannose-type oligosaccharides using high-field NMR spectroscopy combined with 13C-labeling technique
  • Author(s): Kotaro Yanagi, Yukiko Kamiya, Toshihiko Kitajima, Takumi Yamaguchi, Yasunori Chiba and Koichi Kato
  • Organizer: 4th Asian Communications of Glycobiology and Glycotechnology (ACGG 2012 Conference)
  • Place of Presentation: Jeju (Korea)
• [Presentation] 常磁性効果を応用した糖鎖の動的立体構造解析
  • Author(s): 山口拓実，Zhang Ying，山本さよこ，亀田倫史，加藤晃一
  • Organizer: 第51回 NMR討論会
  • Place of Presentation: ウインクあいち（愛知）
• [Presentation] NMR法による神経変性疾患関連タンパク質とガングリオシドクラスターとの相互作用解析
  • Author(s): 矢木真穂，山口拓実，植草義徳，加藤晃一
  • Organizer: 第34回 生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 京都大学（京都）
• [Presentation] NMR spectroscopic approaches to the conformational dynamics of oligosaccharides by paramagnetic tagging
  • Author(s): Takumi Yamaguchi, Ying Zhang, Koichi Kato
  • Organizer: The First International Symposium on Biofunctional Chemistry
  • Place of Presentation: 東工大蔵前会館（東京）
• [Presentation] Conformations, dynamics, and interactions of sugar chains as studied by NMR spectroscopy
  • Author(s): Yoshinori Uekusa, Ying Zhang, Kotaro Yanagi, Takumi Yamaguchi, Koichi Kato
  • Organizer: The 6th International Symposium, Molecular Science of Fluctuations toward Biological Functions
  • Place of Presentation: 京都テルサ（京都）
• [Presentation] Characterization of conformational dynamics of branched oligosaccharides by using paramagnetic NMR techniques
  • Author(s): Ying Zhang, Takumi Yamaguchi, Sayoko Yamamoto, Koichi Kato
  • Organizer: 9th SOKENDAI Student Seminar (Life Science Retreat 2012)
  • Place of Presentation: ヤマハリゾートつま恋（静岡）
• [Presentation] Comparative conformational analysis of high-mannose-type oligosaccharides using high-field NMR spectroscopy combined with 13C-labeling technique
  • Author(s): Kotaro Yanagi, Yukiko Kamiya, Toshihiko Kitajima, Takumi Yamaguchi, Yasunori Chiba, Koichi Kato
  • Organizer: Sokendai Asian Winter School "Frontiers in Photo-Molecular Science"
  • Place of Presentation: 岡崎コンファレンスセンター（愛知）
• [Presentation] Paramagnetic Lanthanide-tagging for NMR Conformational Characterization of Glycolipids
  • Author(s): Takumi Yamaguchi, Ying Zhang, Koichi Kato
  • Organizer: Pure and Applied Chemistry International Conference 2013 (PACCON 2013)
  • Place of Presentation: Chon Buri (Thailand)
• [Presentation] NMR approaches to the molecular basis of oligosaccharide functions
  • Author(s): Takumi Yamaguchi, Koichi Kato
  • Organizer: 2013 Asian Core Winter School
  • Place of Presentation: Busan (Korea)
  • Invited
• [Book] Advances in Experimental Medicine and Biology (2015)
  • Author(s): Y. Zhang, T. Yamaguchi, T. Satoh, M. Yagi-Utsumi, Y. Kamiya, Y. Sakae Y. Okamoto, and K. Kato
  • Total Pages: 411
  • Publisher: Springer (Switzerland)
• [Book] Glycoscience: Biology and Medicine (2014)
  • Author(s): T. Yamaguchi, and K. Kato
  • Total Pages: 1568
  • Publisher: Springer (Japan)
• [Book] Advances in Neurobiology (2014)
  • Author(s): Y. Yamaguchi, T. Yamaguchi, and K. Kato
  • Total Pages: 584
  • Publisher: Springer (New York)
• [Remarks] 水中で絶え間なく揺らいでいる糖鎖の立体構造を描き出す
  • URL: https://www.ims.ac.jp/news/2014/09/05_2994.html