Elucidation of the weak interaction-triggered system of proteins and its design proposal
| Project/Area Number |
18H02082
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
黒田 大祐 東京大学, 大学院工学系研究科(工学部), 講師 (60756732)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 蛋白質 / 熱力学 / 速度論 / リガンド / 相互作用 / 低分子 / 物理化学 / 蛋白質エンジニアリング / 蛋白質-蛋白質相互作用 / 蛋白質-蛋白質間相互作用 |
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| Outline of Final Research Achievements |
By precisely analyzing the thermodynamics and kinetics of proteins with low binding affinities, I attempted to propose new insights for protein functions into the quality of interactions at low affinity. The interaction analysis of an OMD protein revealed that the function came from an entropy-driven with dehydration. The FcγRIIIa-antibody interaction analysis showed that differences in the variable region and glycosylation, which are not at the binding interface, cause differences in molecular recognition at low affinity. Interaction analysis between the heat shock protein HSP90 and its drug fragment revealed that it has enthalpy-driven with a specific inhibitory activity despite its low binding affinity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果より、低親和性相互作用の特異性が、熱力学的パタメータと速度論パラメータを精密に解析することにより理解することできることが明らかになった。実際の生体内の蛋白質相互作用の結合親和性には、microMレベルの低親和性が多種多様に存在する。細胞システムにおける蛋白質間相互作用の秩序は、平衡定数のみでは正確に記述できない、理解することができないのではない、低親和性相互作用による生体分子の秩序がある可能性がある。ここに生命システムの本質を理解する新しい観点があると考えられ、これより新規の生命分子制御剤のコンセプトを打ち出す指針になるであろう。
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Report
(4 results)
Research Products
(85 results)
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[Journal Article] A Peptoid with Ectended Shape in Water2019
Author(s)
Morimoto J, Fukuda Y, Kuroda D, Watanabe T, Yoshida F, Asada M, Nakamura T, Senoo A, Nagatoishi S, Tsumoto K, *Sando S
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Journal Title
J Am Chem Soc.
Volume: 141
Issue: 37
Pages: 14612-14623
DOI
Related Report
Peer Reviewed
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[Journal Article] Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction.2019
Author(s)
Nonaka H, Nakanishi Y, Kuno S, Ota T, Mochidome K, Saito Y, Sugihara F, Takakusagi Y, Aoki I, Nagatoishi S, Tsumoto K, Sando S.
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Journal Title
Nat Commun.
Volume: 10(1)
Issue: 1
Pages: 876-876
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] My research in Tokyo2020
Author(s)
Valenciano-Bellido Sandra, Caaveiro Jose M.M, Nakakido M, Nagatoishi S and Tsumoto K
Organizer
I Iberoamerican research encounter in Japan (organized by ACE Japón, Spanish Embassy and Instituto Cervantes)
Related Report
Int'l Joint Research
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