Molecular Dynamics and Combined QM/MM Studies on the Deactivation of anti-Tubercular Drug Isoniazid by Arylamine N-Acetyltransferases

被引：0

作者：

乔青安 ^{[1
]}

马翠华 ^{[1
]}

宋慧玲 ^{[1
]}

蔡红兰 ^{[1
]}

蔡政亭 ^{[2
]}

冯大诚 ^{[2
]}

机构：

[1] School of Chemistry and Materials Science,Ludong University

[2] Institute of Theoretical Chemistry,Shandong University

来源：

结构化学 | 2012年 / 31卷 / 05期

基金：

中国国家自然科学基金;

关键词：

NATs; QM/MM method; deactivation of isoniazid; acetyl group transfer;

D O I：

暂无

中图分类号：

O621.29 [];

学科分类号：

070303 ; 081704 ;

摘要：

Both a molecule dynamic study and a combined quantum mechanics and mole-cule mechanics(QM/MM) study on the acetylating deactivation mechanism of isoniazid were presented.This type of reaction was catalyzed by arylamine N-acetyltransferases(NATs) and the results strongly support a direct acetyl group transfer process rather than a stepwise one.The isoniazid was strictly restrained in proper relative position to accept the acetyl group by a Hydrogen-bond network formed by the residues at the active center.The residues,His110 and Cys70,would be functioned as ’general base’ rather than ’general acid’.If all the residues(including H2O molecules) were removed from the system,the activation energy will be increased from 145.1 to 243.3 kJ/mol.The calculations met the experimental data with good agreement.

引用

页码：683 / 689

页数：7