Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction

doi:10.1002/(SICI)1097-461X(1999)74:3<315::AID-QUA4>3.0.CO;2-Y

	Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction
	Wang, QM ; Jiang, HL; Chen, KX; Ji, RY ; Ye, YJ
刊名	INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
	1999-08-15
卷号	74 期号:3 页码:315-325
关键词	acetylcholinesterase deacylation process transition state catalytic mechanism stepwise mechanism cooperative mechanism
ISSN号	0020-7608
DOI	10.1002/(SICI)1097-461X(1999)74:3<315::AID-QUA4>3.0.CO;2-Y
文献子类	Article
英文摘要	Acetylcholinesterase (AChE)-catalyzed hydrolysis of the neurotransmitter, acetylcholine (ACh), occurs via an acylation and deacylation process. The deacylation process was studied theoretically by the semiempirical quantum chemical method AM1 using the model molecules. To investigate the micro features of the deacylation process, two types of possible reaction mechanisms, the stepwise mechanism and the cooperative mechanism, were proposed and studied. All optimized structures of the model molecules for the possible reactants, intermediates, transition states, and products in the reaction pathway of the two possible mechanisms were obtained. Energy profiles and the structural properties of the transition states indicated that the deacylation process proceeds through the cooperative mechanism, that is, the proton transfer from H2O to His440 occurs simultaneously with the nucleophilic attack of the oxygen atom of the H2O to the carbonyl carbon of the acylenzyme. Considering the reaction mechanism of acylation, the first process in AChE-catalyzed hydrolysis of ACh, studied in our previous article, we can conclude that both the acylation and deacylation process limit the rate of the entire AChE-catalyzed reaction. Four transition states exist in the whole pathway of the AChE-catalyzed reaction. The rehybridization of the transition state was found. These results are in agreement with the kinetics data and the secondary isotope effects of AChE-catalyzed reactions. (C) 1999 John Wiley & Sons, Inc.
WOS关键词	TRANSITION-STATE STRUCTURE ; ACETYLCHOLINESTERASE ; HYDROLYSIS ; SIMULATION ; ACYLATION ; DYNAMICS
WOS研究方向	Chemistry ; Mathematics ; Physics
语种	英语
出版者	JOHN WILEY & SONS INC
WOS记录号	WOS:000081626900004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274708]
专题	中国科学院上海药物研究所
通讯作者	Jiang, HL
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab New 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, KX,et al. Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction[J]. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,1999,74(3):315-325.
APA	Wang, QM,Jiang, HL,Chen, KX,Ji, RY,&Ye, YJ.(1999).Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction.INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY,74(3),315-325.
MLA	Wang, QM,et al."Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction".INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 74.3(1999):315-325.