Density Functional Theory Study on the Histidine-assisted Mechanism of Arylamine N-Acetyltransferase Acetylation

作     者：乔青安 高善民 靳月庆 陈鑫 孙孝敏 杨传路 

作者机构：School of Chemistry and Materials ScienceLudong University Library of Ludong University College of Life ScienceShandong University School of Physics and Electronic EngineeringLudong University 

出 版 物：《Chinese Journal of Structural Chemistry》 (结构化学（英文）)

年 卷 期：2008年第27卷第9期

页      面：1127-1133页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：the National Natural Scientific Foundation of China(No.20603030) the Youth Natural Science Foundation of Ludong University(No.042902) the Post-doctor Research Foundation of Shandong Province(No.200601007) the Youth Natural Science Foundation of Shandong Provincial Education Department(No.200139) 

主　　题：arylamine N-acetyltransferase density functional theory acetyl group transfer histidine-assisted mechanism 

摘      要：Arylamine N-acetyltransferases （NATs, EC 2.***.1.5） catalyze the N-acetylation of primary arylamines, and play a key role in the biotransformation and metabolism of drugs, carcinogens, etc. In this paper, three possible reaction mechanisms are investigated and the results indicate that if the acetyl group directly transfers from the donor to the acceptor, the high activation energies will make it hard to obtain the target products. When using histidine to mediate the acetylation process, these energies will drop in the 15-45 kJ/mol range. If the histidine residue is protonated, the corresponding energies will be decreased by about 35-87 kJ/mol. The calculations predict an enzymatic acetylation mechanism that undergoes a thiolate-imidazolium pair, which agrees with the experimental results very well.