| Project/Area Number |
18K05345
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Ishiwata Akihiro 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (70342748)
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| Co-Investigator(Kenkyū-buntansha) |
張 恵平 国立研究開発法人理化学研究所, 放射光科学研究センター, 研究員 (10462706)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 合成糖鎖 / 酵素 / 糖鎖-タンパク質複合体 / NMR / 相互作用解析 / 有機合成化学 / 生体分子 / 構造解析 / 糖鎖 / NMR 相互作用解析 |
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| Outline of Final Research Achievements |
The project entitled “Study on synthetic glycans complexed with glycosidase foe NMR analysis of the active site“ focused on a) chemical synthesis of enzyme substrate glycans and b) analysis using analytical methods. Preparation of a complex arabinan fragment substrate, structural analysis of the obtained substrate in solution state without enzyme, and estimation of the cleavage site specificity have been conducted. It was considered difficult to evaluate the detailed binding motif by NMR method with our system studied this time due to week binding between the glycan-linked probe and the enzyme. The functional analysis of a series of the new arabinan-degrading enzymes, however, could be performed by combining the enzyme reaction monitoring by NMR, the analysis of binding of the ligand probes to active site and novel carbohydrate binding motif from the crystal structure of the substrate-enzyme complex, and the structural analysis of the unexpected product.
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| Academic Significance and Societal Importance of the Research Achievements |
結核菌類細胞壁糖鎖成分の均一な糖鎖やプローブ類をデザインし合成することにより、新規酵素との分子レベルでの相互作用解析にを駆使しより詳細な機能解明を達成する手法を示すことができた。近年遺伝子やアミノ酸シークエンス検索により著しく加速してきている新規酵素探索にその機能解析を組み合わせたブレイクスルーとなると考えている。ミコバクテリアのAGPやLAMの再利用に関する分子レベルでの研究やアラビナン-酵素に関する構造解析等の報告例はごくわずかであり、新たな薬剤の開発への糸口を示した。
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