On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study

doi:10.1002/(SICI)1097-461X(1998)70:3<515::AID-QUA7>3.0.CO;2-X

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study
	Wang, QM ; Jiang, HL; Chen, JZ ; Chen, KX; Ji, RY
刊名	INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
	1998-10-05
卷号	70 期号:3 页码:515-525
关键词	acetylcholinesterase acylation process transition state quantum chemistry catalytic mechanism
ISSN号	0020-7608
DOI	10.1002/(SICI)1097-461X(1998)70:3<515::AID-QUA7>3.0.CO;2-X
文献子类	Article
英文摘要	The acylation process in the acetylcholinesterase (AChE)-catalyzed hydrolysis of the neurotransmitter, acetylcholine (ACh), has been determined with the semiempirical quantum chemical calculation method AM1 using the model molecules extracted from the X-ray crystal structure of Torpedo Californica AChE. For the sake of identifying the microfeatures of the mechanism of this reaction, two types of possible mechanisms, stepwise mechanism and cooperative mechanisms, were proposed and studied with AM1 methods. All the model molecules for the possible reactants, intermediates, transition states, and products in the reaction pathways of the two mechanisms were obtained. Energy profiles, the structural properties of the transition states, indicate that the acylation of AChE-catalyzed hydrolysis of ACh adopts the cooperative mechanism, i.e., the proton transfer from Ser220 of AChE to His440 occurs simultaneously with the nucleophilic attack of Ser200 to the carbonyl carbon atom of ACh. This result is in agreement with the kinetic data and the secondary isotope effects of AChE-catalyzed reactions. (C) 1998 John Wiley & Sons, Inc.
WOS关键词	TRANSITION-STATE STRUCTURE ; REACTION DYNAMICS ; ACETYLCHOLINESTERASE ; ANILIDES
WOS研究方向	Chemistry ; Mathematics ; Physics
语种	英语
出版者	JOHN WILEY & SONS INC
WOS记录号	WOS:000076524600007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274800]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Jiang, HL
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Inst Biophys, Dept Prot Engn, Beijing 100101, Peoples R China
推荐引用方式 GB/T 7714	Wang, QM,Jiang, HL,Chen, JZ,et al. On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study[J]. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,1998,70(3):515-525.
APA	Wang, QM,Jiang, HL,Chen, JZ,Chen, KX,&Ji, RY.(1998).On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study.INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,70(3),515-525.
MLA	Wang, QM,et al."On the possible reaction pathway for the acylation of AChE-catalyzed hydrolysis of ACh: Semiempirical quantum chemical study".INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 70.3(1998):515-525.