Structural Switching of Staphylococcus aureus Clp Protease A KEY TO UNDERSTANDING PROTEASE DYNAMICS

doi:10.1074/jbc.M111.277848

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	Structural Switching of Staphylococcus aureus Clp Protease A KEY TO UNDERSTANDING PROTEASE DYNAMICS
	Zhang, Jie; Ye, Fei; Lan, Lefu; Jiang, Hualiang; Luo, Cheng; Yang, Cai-Guang
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2011-10-28
卷号	286 期号:43 页码:37590-37601
ISSN号	0021-9258
DOI	10.1074/jbc.M111.277848
文献子类	Article
英文摘要	ATP-dependent Clp protease (ClpP) is an attractive new target for the development of anti-infective agents. The ClpP protease consists of two heptameric rings that enclose a large chamber containing 14 proteolytic active sites. Recent studies indicate that ClpP likely undergoes conformational switching between an extended and degraded active state required for substrate proteolysis and a compacted and catalytically inactive state allowing product release. Here, we present the wild-type ClpP structures in two distinct states from Staphylococcus aureus. One structure is very similar to those solved ClpP structures in the extended states. The other is strikingly different from both the extended and the compacted state as observed in ClpP from other species; the handle domain of this structure kinks to take on a compressed conformation. Structural analysis and molecular dynamic simulations show that the handle domain predominantly controls the way in which degradation products exit the chamber through dynamic conformational switching from the extended state to the compressed state. Given the highly conserved sequences among ClpP from different species, this compressed conformation is unexpected and novel, which is potentially valuable for understanding the enzymatic dynamics and the acting mechanisms of ClpP.
资助项目	National Natural Science Foundation of China[20972173] ; National Natural Science Foundation of China[20972174] ; National Natural Science Foundation of China[90913010] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[21172234] ; Chinese Academy of Sciences[XDA01040305] ; Science and Technology Commission of Shanghai Municipality[09PJ1411600] ; Science and Technology Commission of Shanghai Municipality[10410703900] ; Key Project of Chinese National Programs for Fundamental Research and Development[2009CB918502] ; National Science and Technology Major Project[2009ZX09301-001]
WOS关键词	ESCHERICHIA-COLI CLPP ; DEPENDENT PROTEASES ; MAXIMUM-LIKELIHOOD ; STRESS TOLERANCE ; ATP HYDROLYSIS ; ACTIVE-SITE ; N-TERMINUS ; MODEL ; ANTIBIOTICS ; COMPLEXES
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000296542400057
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278365]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室药理学第三研究室药理学第一研究室
通讯作者	Luo, Cheng
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jie,Ye, Fei,Lan, Lefu,et al. Structural Switching of Staphylococcus aureus Clp Protease A KEY TO UNDERSTANDING PROTEASE DYNAMICS[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(43):37590-37601.
APA	Zhang, Jie,Ye, Fei,Lan, Lefu,Jiang, Hualiang,Luo, Cheng,&Yang, Cai-Guang.(2011).Structural Switching of Staphylococcus aureus Clp Protease A KEY TO UNDERSTANDING PROTEASE DYNAMICS.JOURNAL OF BIOLOGICAL CHEMISTRY,286(43),37590-37601.
MLA	Zhang, Jie,et al."Structural Switching of Staphylococcus aureus Clp Protease A KEY TO UNDERSTANDING PROTEASE DYNAMICS".JOURNAL OF BIOLOGICAL CHEMISTRY 286.43(2011):37590-37601.