Structure-based computational study of the hydrolysis of New Delhi metallo-beta-lactmase-1

doi:10.1016/j.bbrc.2012.12.141

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	Structure-based computational study of the hydrolysis of New Delhi metallo-beta-lactmase-1
	Zhu, Kongkai 1,3; Lu, Junyan 1; Ye, Fei 1; Jin, Lu 1; Kong, Xiangqian 1; Liang, Zhongjie 2; Chen, Yong 3; Yu, Kunqian1 ; Jiang, Hualiang1 ; Li, Jun-Qian 3
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2013-02-01
卷号	431 期号:1 页码:2-7
关键词	New Delhi metallo-beta-lactmase-1 Metallo-beta-lactamase Molecular dynamics simulations Molecular mechanics/Poisson-Boltzmann surface area
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2012.12.141
文献子类	Article
英文摘要	New Delhi metallo-beta-lactmase-1 (NDM-1) is an enzyme that confers antibiotic resistance to bacteria and is thus a serious threat to human health. Almost all clinically available beta-lactam antibiotics can be hydrolyzed by NDM-1. To determine the mechanism behind the wide substrate diversity and strong catalytic ability of NDM-1, we explored the molecular interactions between NDM-1 and different beta-lactam antibiotics using computational methods. Molecular dynamics simulations and binding free energy calculations were performed on enzyme-substrate (ES) complex models of NDM-1-Meropenem, NDM-1-Nitrocefin, and NDM-1-Ampicillin constructed by molecular docking. Our computational results suggest that mutant residues Ile35 and Lys216, and active site loop L1 residues 65-73 in NDM-1 play crucial roles in substrate recognition and binding. The results of our study provide new insights into the mechanism behind the enhanced substrate binding and wider substrate spectrum of NDM-1 compared with its homologous enzymes CcrA and IMP-1. These insights may be useful in the discovery and design of specific and potent inhibitors against NDM-1. (C) 2013 Elsevier Inc. All rights reserved.
资助项目	National High Technology Research and Development Program of China[2012AA020302] ; National High Technology Research and Development Program of China[2012AA020301] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[21073034] ; Key Project of Chinese National Programs for Fundamental Research and Development[2009CB918502] ; Natural Science Foundation of the Fujian Province[2010J05023] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507-004]
WOS关键词	METALLO-BETA-LACTAMASE ; BACTEROIDES-FRAGILIS ; MOLECULAR-DYNAMICS ; RESISTANCE ; MECHANISM ; NDM-1 ; INHIBITORS ; CATALYSIS ; BINDING ; CCRA
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000315428800001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277740]
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
通讯作者	Chen, Yong
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Jiangsu, Peoples R China 3.Fuzhou Univ, Dept Chem, Fuzhou 350108, Fujian, Peoples R China;
推荐引用方式 GB/T 7714	Zhu, Kongkai,Lu, Junyan,Ye, Fei,et al. Structure-based computational study of the hydrolysis of New Delhi metallo-beta-lactmase-1[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2013,431(1):2-7.
APA	Zhu, Kongkai.,Lu, Junyan.,Ye, Fei.,Jin, Lu.,Kong, Xiangqian.,...&Luo, Cheng.(2013).Structure-based computational study of the hydrolysis of New Delhi metallo-beta-lactmase-1.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,431(1),2-7.
MLA	Zhu, Kongkai,et al."Structure-based computational study of the hydrolysis of New Delhi metallo-beta-lactmase-1".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 431.1(2013):2-7.