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Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues

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成果类型:
期刊论文、会议论文
作者:
Pei-Liang Zhao;Le Wang;Xiao-Lei Zhu;Xiaoqin Huang;Chang-Guo Zhan;...
通讯作者:
Zhan, Chang-Guo
作者机构:
[Guang-Fu Yang; Xiao-Lei Zhu; Pei-Liang Zhao] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Coll Chem, Minist Educ, Wuhan 430079, Peoples R China.
[Chang-Guo Zhan; Xiaoqin Huang] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA.
[Jia-Wei Wu; Le Wang] Tsinghua Univ, Key Lab Bioinformat, Dept Biol Sci & Biotechnol, MOE, Beijing 100084, Peoples R China.
[Chang-Guo Zhan] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, 725 Rose St, Lexington, KY 40536 USA.
通讯机构:
[Zhan, Chang-Guo] U
Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, 725 Rose St, Lexington, KY 40536 USA.
语种:
英文
关键词:
Inhibitor;Cytochrome;Interaction
期刊:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN:
0002-7863
年:
2010
卷:
132
期:
1
页码:
185-194
会议名称:
International conference of molecular simulations and applied informatics technologies
会议论文集名称:
The 5th International conference of molecular simulations and applied informatics technologies : [Life science articles proceedings]
会议时间:
2010-01-01
会议地点:
Wuhan(CN)
会议赞助商:
中国化学会<&wdkj&>华中师范大学<&wdkj&>创腾科技有限公司<&wdkj&>中科院上海药物研究所
基金类别:
National Basic Research Program of ChinaNational Basic Research Program of China [201OCB126103]; NSFCNational Natural Science Foundation of China (NSFC) [20925206, 20932005, 20872045]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RC1MH088480]; NATIONAL INSTITUTE OF MENTAL HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [RC1MH088480, RC1MH088480] Funding Source: NIH RePORTER
机构署名:
本校为第一机构
院系归属:
化学学院
摘要:
Cytochrome bc1 complex (EC 1.10.2.2, bc1), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target* for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc1 complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective n-n interactions, whereas the side chai...

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