Quantum chemistry study on the interaction of the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases

doi:10.1021/jp013336j

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Quantum chemistry study on the interaction of the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases
	Cheng, F ; Zhang, RH ; Luo, XM; Shen, JH; Li, X ; Gu, JD; Zhu, WL; Shen, JK ; Sagi, I ; Ji, RY
刊名	JOURNAL OF PHYSICAL CHEMISTRY B
	2002-05-02
卷号	106 期号:17 页码:4552-4559
ISSN号	1520-6106
DOI	10.1021/jp013336j
文献子类	Article
英文摘要	Six zinc complexes, Zn(imidazole)(3)X (where X = water, CH3S-, hydroxamate, formylhydroxylamine, hypophosphite, and acetate), have been calculated with the density functional theory (DFT) method B3LYP/6-31G* to probe the interaction between the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases (MMPs). According to our calculation, their interaction modes can be divided into three classes. The structural features of these complexes are in agreement with the X-ray data in the Cambridge Structural Database and the Protein Data Bank. The atomic charge analyses proved that the catalytic water molecule in the active site of MMPs can be activated after coordinating with the zinc ion and thus acts as a good nucleophile to attack and degrade the substrate of MMPs. The geometric parameters of these complexes, the charge transfers from the exogenous ligands to the Zn(II), and the calculated relative binding, free energy characterize well the binding ability of these ligands with the zinc ion. The inhibitory activities of the MMP inhibitors, which contain the same substituents and different zinc binding groups (ZBGs), correlate well with the binding free energies predicted by the DFT calculation with correlation coefficients of 0.969 for matrilysin and 0.939 for human fibroblast collagenase (HFC). This gives a possible good strategy for predicting the inhibitory activity for the newly designed inhibitors of MMPs; those potential inhibitors that would exhibit strong binding ability of ZBGs to Zn(II) using this paradigm would therefore be expected to have greater inhibitory activity.
WOS关键词	DRUG DESIGN ; CRYSTAL-STRUCTURES ; INHIBITORS
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000175356900029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274362]
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	Jiang, HL
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,State Key Lab Drug Res, Ctr Drug Discovery & Design, Shanghai 200031, Peoples R China 2.Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel
推荐引用方式 GB/T 7714	Cheng, F,Zhang, RH,Luo, XM,et al. Quantum chemistry study on the interaction of the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2002,106(17):4552-4559.
APA	Cheng, F.,Zhang, RH.,Luo, XM.,Shen, JH.,Li, X.,...&Jiang, HL.(2002).Quantum chemistry study on the interaction of the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases.JOURNAL OF PHYSICAL CHEMISTRY B,106(17),4552-4559.
MLA	Cheng, F,et al."Quantum chemistry study on the interaction of the exogenous ligands and the catalytic zinc ion in matrix metalloproteinases".JOURNAL OF PHYSICAL CHEMISTRY B 106.17(2002):4552-4559.