Computational modeling and analysis of glycosyl hyrolases : reaction mechanism and catalytic design
| Project/Area Number |
18K05052
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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 32010:Fundamental physical chemistry-related
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
Toyokazu ISHIDA 国立研究開発法人産業技術総合研究所, 材料・化学領域, 主任研究員 (70443166)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 理論計算化学 / QM/MM計算 / 分子動力学計算 / 自由エネルギー計算 / 酵素反応機構 / バイオマス分解酵素 / Glycoside hydrolase (GH) / キシラナーゼ（Xylanase） / キシラナーゼ (Xylanase) / 基底状態不安定化 / 基質歪み / Glycoside hydrolase(GH) / グリコシル化反応 / 基質不安定化 / 電子状態計算 / 複合シミュレーション / 反応遷移状態/中間体 / 酵素機能改変 |
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| Outline of Final Research Achievements |
In this research project we have investigated the reaction mechanism of GH11 xylanase, a typical biomass-decomposing enzyme which catalyzes the hydrolysis of lignocellulosic hemicellulose (xylan), based on the ab initio QM/MM combined with molecular dynamics simulation technique.
For modeling a realistic enzymatic structure, we have employed the recent neutron crystal structure that revealed the protonation states of relevant residues, and we have determined the substrate binding pattern onto the enzymatic active site by using our original QM/MM program. On the basis of the QM/MM free energy profile of glycosylation step, we have identified that the rate-determining step of the glycosylation is a scission of the glycosidic bond after proton transfer from the acidic Glu residue. And also, our QM/MM calculations (free energy barrier as well as secondary kinetic isotope effect) suggest that a reaction intermediate can be transiently formed with short lifetime along the reaction pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
生体内で起こる各種化学反応を触媒するのが酵素であるが、多数の実験構造が解明された現在においてすらその反応機構が完全解明された酵素はなく、酵素の機能改変や新規酵素の分子設計など現代化学が解決すべく問題に対して、分子スケールでの酵素反応機構解明は理論計算化学分野に課された重要課題の一つとなっている。
自然界に普遍的に存在する酵素の触媒メカニズムを完全に理解し、酵素触媒反応を制御するための化学的知見を提供することは、基礎科学研究において、そして各種化学産業への応用展開も含めて非常に重要な意義を持つ。
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Report
(5 results)
Research Products
(11 results)
