Deciphering molecular mechanism behind conformational change of the Sao Paolo metallo-beta-lactamase 1 by using enhanced sampling

doi:10.1080/07391102.2019.1707121

	Deciphering molecular mechanism behind conformational change of the Sao Paolo metallo-beta-lactamase 1 by using enhanced sampling
	Chen, Jianzhong 2; Wang, Jinan 1; Pang, Laixue 2; Wang, Wei 2; Zhao, Juan 2; Zhu, Weiliang 1
刊名	JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
	2019-12-27
页码	12
关键词	Sao paolo metallo-beta-lactamase-1 REMD simulations normal mode analysis principal component analysis drug resistance of antibiotics
ISSN号	0739-1102
DOI	10.1080/07391102.2019.1707121
通讯作者	Chen, Jianzhong(chenjianzhong1970@163.com) ; Wang, Jinan(jawang@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要	The Sao Paolo metallo-beta-lactamase-1 (SPM-1) plays an important role in drug resistance of beta-lactam antibiotics and bindings of zinc ions produce significant effect on the conformations of SPM-1. Thus, it is of significance for understanding function of SPM-1 to probe the conformational changes of SPM-1 induced by bindings of zinc ions. Because replica-exchange molecular dynamics (REMD) simulations can efficiently improve conformational samplings of proteins, REMD and normal mode analysis (NMA) were performed on three systems, including SPM-1 with non-zinc ions, single zinc ion and double zinc ions, to decipher molecular mechanism of conformational changes for SPM-1. The results suggest that binding of double zinc ions induces a closed state of SPM-1, while SPM-1 with binding of non-zinc and single zinc ion mainly exists as an open conformation. The analysis of interaction network between residues was carried out by using the program Ring 2.0. The results show that binding of double zinc ions highly enhances the stability of the pi-pi interaction network consisting of F60, Y61, F82, F152, Y153 and Y226, two hydrogen bonds between E83 and R161 as well as the salt bridge interaction between E151 and K159 compared to the SPM-1 with non-zinc or single zinc ion, which better stabilizes the closed conformation of SPM-1. Thus, the closed conformation of SPM-1 induced by bindings of double zinc ions is important in catalysis and determining inhibitor selectivity. Meanwhile, this work may provide useful theoretical hints for design of potent inhibitors toward drug resistance of beta-lactam antibiotics. Communicated by Ramaswamy H. Sarma.
资助项目	National Key Research and Development Program[2016YFA0502301] ; National Natural Science Foundation of China[21403283] ; National Natural Science Foundation of China[81573350] ; National Natural Science Foundation of China[11504206] ; Shandong Provincial Natural Science Foundation[ZR2017MA040] ; key research and development project of Shandong province[2019GGX102050]
WOS关键词	NORMAL-MODE ANALYSIS ; PARTICLE MESH EWALD ; REPLICA-EXCHANGE ; FREE-ENERGY ; DYNAMICS SIMULATIONS ; TRANSITION PATHWAY ; SUBSTRATE-BINDING ; CRYSTAL-STRUCTURE ; COMPLEX-FORMATION ; INSIGHTS
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	TAYLOR & FRANCIS INC
WOS记录号	WOS:000504611000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282228]
专题	中国科学院上海药物研究所
通讯作者	Chen, Jianzhong; Wang, Jinan; Zhu, Weiliang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Shandong Jiaotong Univ, Sch Sci, Jinan 250357, Shandong, Peoples R China
推荐引用方式 GB/T 7714	Chen, Jianzhong,Wang, Jinan,Pang, Laixue,et al. Deciphering molecular mechanism behind conformational change of the Sao Paolo metallo-beta-lactamase 1 by using enhanced sampling[J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,2019:12.
APA	Chen, Jianzhong,Wang, Jinan,Pang, Laixue,Wang, Wei,Zhao, Juan,&Zhu, Weiliang.(2019).Deciphering molecular mechanism behind conformational change of the Sao Paolo metallo-beta-lactamase 1 by using enhanced sampling.JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,12.
MLA	Chen, Jianzhong,et al."Deciphering molecular mechanism behind conformational change of the Sao Paolo metallo-beta-lactamase 1 by using enhanced sampling".JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2019):12.