Reaction Mechanism of Actin ATP Hydrolysis Studied by QM/MM Calculations  

作　　者：WANG Yiwen LIN Lirui XU Li-Yan LI En-Min DONG Geng 

机构地区：[1]Department of Biochemistry and Molecular Biology,Shantou University Medical College,Shantou,515041,P.R.China [2]Department of Bioinformatics,Shantou University Medical College,Shantou,515041,P.R.China [3]Medical Informatics Research Center,Shantou University Medical College,Shantou,515041,P.R.China [4]Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Area of Guangdong Higher Education Institutes,Shantou University Medical College,Shantou,515041,P.R.China [5]Cancer Research Center,Shantou University Medical College,Shantou,515041,P.R.China [6]Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology,Shantou University Medical College,Shantou,515041,P.R.China

出　　处：《Chemical Research in Chinese Universities》2024年第5期849-855,共7页高等学校化学研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.21907063),the Li Ka-shing Foundation,China(No.LD0101),the 2020 Li Ka-shing Foundation Cross-Disciplinary Research Grant,China(No.2020LKSFG07B);the Innovation Team Grant of Department of Education of Guangdong Provice,China(No.2021KCXTD005);the Shantou University Medical College(SUMC)Scientific Research Initiation Grant,China(No.510858063).

摘　　要：Actin fibers are an important part of the cytoskeleton,providing vital support for the plasma membrane.This function is driven by its ATPase(ATP:adenosine triphosphate)activity,i.e.,ATP+H_(2)O→ADP+Pi.This seemingly simple reaction has attracted much attention because the hydrolysis of ATP provides energy to support life processes.However,the reaction mechanism of ATP hydrolysis in actin is not clear.In order to gain deep insights into the functions of actin,it is essential to elucidate the reaction mechanism of the actin ATP hydrolysis.In this paper,we have studied the reaction mechanism of the ATP hydrolysis in actin by the combined quantum mechanical and molecular mechanics(QM/MM)calculations.Our results show that 1)bond cleavage of the Pγ—OS of ATP and bond formation between oxygen of the lytic water and Pγatoms take place simultaneously,and this is the rate-limiting step of the hydrolysis;2)the proton on the lytic water transfers to the phosphate to form H_(2)P_(γ)O_(4)−via one bridge water.The energy barrier of the complete reaction is 17.6 kcal/mol(1 kcal=4.184 kJ),which is in high agreement with the experimental value.

关 键 词：ACTIN Adenosine triphosphate(ATP)hydrolysis Quantum mechanical and molecular mechanics(QM/MM) Reaction mechanism 

分 类 号：R318[医药卫生—生物医学工程] TP39[医药卫生—基础医学]