标题:QM/MM Study on the Reaction Mechanism of O~6-AlkyIguanine-DNA Alkyltransferase
作者:Qianqian Hou;Likai Du;Jun Gao
作者机构:[Hou, Q] Key Lab of Colloid and Interface Chemistry, Shandong University, Ministry of Education, Jinan, Shandong 250100, China;[ Du, L] Key Lab of Col 更多
通讯作者:Liu, Y
通讯作者地址:[Liu, YJ]Shandong Univ, Key Lab Colloid & Interface Chem, Minist Educ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China.
来源:The journal of physical chemistry, B. Condensed matter, materials, surfaces, interfaces & biophysical
出版年:2010
卷:114
期:46
页码:15296-15300
DOI:10.1021/jp106714m
摘要:Combined quantum-mechanical/molecular-mechanical (QM/MM) approaches have been applied to investigate the detailed reaction mechanism of human O~6-alkylguanine-DNA alkyltransferase (AGT). AGT is a direct DNA repair protein that is capable of repairing alkylated DNA by transferring the methyl group to the thiol group of a cysteine residue (Cys145) in the active site in an irreversible and stoichiometric reaction. Our QM/MM calculations reveal that the methyl group transferring step is expected to occur through two steps, in which the methyl carbocation generating step is the rate-determining step with an energy barrier of 14.4 kcal/mol at the QM/MM B3LYP/6-31G(d,p)//CHARMM22 level of theory. It is different from the previous theoretical studies based on QM calculations by using a cluster model in which the methyl group transferring step is a one-step process with a higher energy barrier.
收录类别:EI;SCOPUS;SCIE
WOS核心被引频次:6
Scopus被引频次:8
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-78649598850&doi=10.1021%2fjp106714m&partnerID=40&md5=5572c45e37d20f45bc3a885250d70a81
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