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Helix Unfolding/Refolding Characterizes the Functional Dynamics of Staphylococcus aureus Clp Protease

文献类型：期刊论文

作者Ye, Fei2; Zhang, Jie2; Liu, Hongchuan2; Hilgenfeld, Rolf2,3; Zhang, Ruihan2; Kong, Xiangqian2; Li, Lianchun2; Lu, Junyan2; Zhang, Xinlei2,4; Li, Donghai1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
出版日期2013-06-14
卷号288期号:24页码:17643-17653
ISSN号0021-9258
DOI10.1074/jbc.M113.452714
文献子类Article
英文摘要The ATP-dependent Clp protease (ClpP) plays an essential role not only in the control of protein quality but also in the regulation of bacterial pathogen virulence, making it an attractive target for antibacterial treatment. We have previously determined the crystal structures of Staphylococcus aureus ClpP (SaClpP) in two different states, extended and compressed. To investigate the dynamic switching of ClpP between these states, we performed a series of molecular dynamics simulations. During the structural transition, the long and straight helix E in the extended SaClpP monomer underwent an unfolding/refolding process, resulting in a kinked helix very similar to that in the compressed monomer. As a stable intermediate in the molecular dynamics simulation, the compact state was suggested and subsequently identified in x-ray crystallographic experiment. Our combined studies also determined that Ala(140) acted as a "hinge" during the transition between the extended and compressed states, and Glu(137) was essential for stabilizing the compressed state. Overall, this study provides molecular insights into the dynamics and mechanism of the functional conformation changes of SaClpP. Given the highly conserved sequences of ClpP proteins among different species, these findings potentially reflect a switching mechanism for the dynamic process shared in the whole ClpP family in general and thus aid in better understand the principles of Clp protease assembly and function.
WOS关键词ESCHERICHIA-COLI ; ENERGY LANDSCAPE ; STRESS TOLERANCE ; BETA-LACTONES ; ACTIVE-SITE ; RECOGNITION ; VIRULENCE ; BACTERIAL ; ANTIBIOTICS ; PROTEINS
资助项目National High Technology Research and Development Program of China[2012AA020302] ; National Natural Science Foundation of China[21172234] ; National Natural Science Foundation of China[90913010] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[21021063] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507-004] ; Key Project of Chinese National Programs for Fundamental Research and Development[2009CB918502] ; Chinese Academy of Sciences Visiting Professorship for Senior International Scientists[2010T1S6] ; Deutsche Forschungsgemeinschaft Cluster of Excellence[306]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000320380600055
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
源URL[http://119.78.100.183/handle/2S10ELR8/277581]  
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
天然药物化学研究室
药理学第三研究室
通讯作者Jiang, Hualiang
作者单位1.Nanjing Univ, Sch Life Sci, Nanjing 210093, Jiangsu, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
3.Univ Lubeck, Ctr Struct & Cell Biol Med, Inst Biochem, D-23538 Lubeck, Germany;
4.Fourth Mil Med Univ, Sch Pharm, Xian 710032, Peoples R China;
5.Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China
推荐引用方式
GB/T 7714		 Ye, Fei,Zhang, Jie,Liu, Hongchuan,et al. Helix Unfolding/Refolding Characterizes the Functional Dynamics of Staphylococcus aureus Clp Protease[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(24):17643-17653.
APA Ye, Fei.,Zhang, Jie.,Liu, Hongchuan.,Hilgenfeld, Rolf.,Zhang, Ruihan.,...&Luo, Cheng.(2013).Helix Unfolding/Refolding Characterizes the Functional Dynamics of Staphylococcus aureus Clp Protease.JOURNAL OF BIOLOGICAL CHEMISTRY,288(24),17643-17653.
MLA Ye, Fei,et al."Helix Unfolding/Refolding Characterizes the Functional Dynamics of Staphylococcus aureus Clp Protease".JOURNAL OF BIOLOGICAL CHEMISTRY 288.24(2013):17643-17653.

入库方式： OAI收割

来源：上海药物研究所

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