QM/MM study on the O_(2)activation reaction of 4-hydroxylphenyl pyruvate dioxygenase reveals a common mechanism forα-ketoglutarate dependent dioxygenase  

作　　者：Linhui Li Suitian Lai Hongyan Lin Xinyun Zhao Xin Li Xi Chen Junjun Liu Guangfu Yang Changguo Zhan 

机构地区：[1]College of Chemistry and Material Science,South-Central Minzu University,Wuhan 430074,China [2]Key Laboratory of Pesticide&Chemical Biology of Ministry of Education,College of Chemistry,Central China Normal University,Wuhan 430079,China [3]School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [4]Department of Pharmaceutical Sciences,College of Pharmacy,University of Kentucky,Lexington,KY 40536,United States

出　　处：《Chinese Chemical Letters》2023年第5期461-465,共5页中国化学快报（英文版）

基　　金：supported by the National Key R&D Program(No.2021YFD1700100);National Natural Science Foundation of China(Nos.21837001,21273089);the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University(No.2018-A01);the Fundamental Research Funds for the Central Universities;the Fundamental Research Funds for the South-Central University for Nationalities(No.CZW20020)。

摘　　要：The dioxygen activation catalyzed by 4-hydorxylphenyl pyruvate dioxygenase(HPPD)were reinvestigated by using hybrid quantum mechanics/molecular mechanics(QM/MM)approaches at the B3LYP/6-311++G(d,p):AMBER level.These studies showed that this reaction consisted of two steps including the dioxygen addition/decarboxylation and hetero O-O bond cleavage,where the first step was found to be rate-determining.The former step initially runs on a septet potential energy surface(PES),then switches to a quintet PES after crossing a septet/quintet minimum energy crossing point(MECP)5-7M2,whereas the rest step runs on the quintet PES.The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier value of 16.9 kcal/mol with available experimental value of 16-17 kcal/mol.The present study challenges the widely accepted view which holds that the O2activation catalyzed byα-keto glutamate(α-KG)dioxygenase mainly runs on the quintet PES and provides new insight into the catalytic mechanism ofα-KG dioxygenase and/or other related Fe(Ⅱ)-dependent oxygenase.

关 键 词：4-Hydroxylphenyl pyruvate dioxygenase O_(2)activation QM/MM Mechanism Minimum energy crossing point 

分 类 号：TQ426.97[化学工程]