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Computational and Experimental Insights into the Mechanism of Substrate Recognition and Feedback Inhibition of Protoporphyrinogen Oxidase

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成果类型:
期刊论文
作者:
Hao, Ge-Fei;Tan, Ying;Yang, Sheng-Gang;Wang, Zhi-Fang;Zhan, Chang-Guo*;...
通讯作者:
Zhan, Chang-Guo
作者机构:
[Yang, Guang-Fu; Yang, Sheng-Gang; Tan, Ying; Wang, Zhi-Fang; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan, Peoples R China.
[Xi, Zhen; Tan, Ying; Wang, Zhi-Fang] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China.
[Zhan, Chang-Guo] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
通讯机构:
[Zhan, Chang-Guo] U
Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
语种:
英文
关键词:
Free energy;Hydrogen bonding;Oxygen;Biochemical simulations;Enzyme kinetics;Binding analysis;Enzyme inhibitors;Enzymes
期刊:
PLOS ONE
ISSN:
1932-6203
年:
2013
卷:
8
期:
7
页码:
e69198-
基金类别:
National Basic Research Program of ChinaNational Basic Research Program of China [2010CB126103]; NSFCNational Natural Science Foundation of China (NSFC) [20902034, 20925206]; National Key Technologies RD ProgramNational Key Technology R&D Program [2011BAE06B05]
机构署名:
本校为第一机构
院系归属:
化学学院
摘要:
Protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) is an essential enzyme catalyzing the last common step in the pathway leading to heme and chlorophyll biosynthesis. Great interest in PPO inhibitors arises from both its significance to agriculture and medicine. However, the discovery of PPO inhibitors with ultrahigh potency and selectivity is hampered due to lack of structural and mechanistic understanding about the substrate recognition, which remains a longstanding question central in porphyrin biology. To understand the mechanism, a novel binding model of protogen (protoporphyrinogen IX, the ...

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