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On the possible reaction pathway for the acylation of AChE‐catalyzed hydrolysis of ACh: Semiempirical quantum chemical study
Author(s) -
Wang Qinmi,
Jiang Hualiang,
Chen Jianzhong,
Chen Kaixian,
Ji Ruyun
Publication year - 1998
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1998)70:3<515::aid-qua7>3.0.co;2-x
Subject(s) - chemistry , acylation , nucleophile , acetylcholinesterase , torpedo , kinetic isotope effect , catalysis , molecule , acetylcholine , computational chemistry , hydrolysis , transition state , reaction mechanism , stereochemistry , organic chemistry , enzyme , acetylcholine receptor , biochemistry , medicine , physics , receptor , deuterium , quantum mechanics , endocrinology
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. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 515–525, 1998