2019 Fiscal Year Final Research Report
Elucidation of enzyme catalytic mechanism regulating transition state by linking conformational change and fluctuations of the active site
| Project/Area Number |
16KT0055
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund |
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| Section | 特設分野 |
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| Research Field |
Transition State Control
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中井 忠志 広島工業大学, 生命学部, 准教授 (00333344)
庄司 光男 筑波大学, 計算科学研究センター, 助教 (00593550)
村川 武志 大阪医科大学, 医学部, 助教 (90445990)
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| Project Period (FY) |
2016-07-19 – 2020-03-31
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| Keywords | ゆらぎ / 酵素 / 反応機構 / 遷移状態 / 中性子構造解析 |
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| Outline of Final Research Achievements |
Neutron crystallography of copper amine oxidase revealed that the cofactor TPQ has both enolate and keto forms on the basis of its protonation state. It is clear that both forms had a distorted ring structure unlike a planner one that has been believed to be taken. The present study also provide detail information for structural changes of the catalytic intermediates during the catalytic cycle. Structural changes, distortion, and fluctuations of the active-site residues and cofactor can control energy level of transition state so that the rate of enzyme-catalyzed reaction is accelerated.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で決定されたアミン酸化酵素の中性子構造は、これまでに報告されている中で最大サイズのタンパク質であり、その新規な活性中心構造を含め、国際的にも高く評価された。また、酵素の触媒反応を加速化させる構造基盤の一端を解明に成功しており、酵素活性中心の動き、歪み、およびゆらぎが遷移状態の影響していることが判明した。その知見は有用酵素の改良にも役立つものと考えられる。
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