| Project/Area Number |
23550035
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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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| Research Field |
Physical chemistry
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
ISHIDA Toyokazu 独立行政法人産業技術総合研究所, ナノシステム研究部門, 研究班長/主任研究員 (70443166)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 酵素反応 / オロチジン一リン酸脱炭酸酵素 / QM/MM計算 / 自由エネルギー計算 / 遷移状態安定化 / 基底状態不安定化 / 相互作用エネルギー解析 / 生体分子シミュレーション / オロチジンーリン酸脱炭酸酵素 / アミノ酸変異 / 理論化学 / 電子状態計算 / 分子動力学計算 |
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| Research Abstract |
Although the general catalytic principle, so-called the transition state stabilization (TST), was proposed over half a century ago, atomistic details of TST have not yet been clarified. Besides TST, other appealing hypotheses, such as the substrate distortion or ground state destabilization (GSD), are still actively debated issues in modern enzymology. One such example is orotidine monophosphate decarboxylase (ODCase), the enzyme that catalyzes the decarboxylation of orotidine monophosphate to uridine monophosphate. To answer the controversial issues, we performed systematic ab initio QM/MM modeling combined with all-electron QM calculation for the entire protein matrix. Our hybrid modeling analyses clearly showed that the reactive substrate has rather distorted geometry, and this distortion can contribute up to 4 kcal/mol energy reduction in the activation process. TST in this case is the key catalytic element, however, GSD can contribute to the catalytic mechanism in ODCase reaction.
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