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

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外文摘要：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+H2O→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 Pγ atomstake 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 H2PγO4-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.

外文关键词：

ActinAdenosine triphosphate(ATP)hydrolysisQuantum mechanical and molecular mechanics(QM/MM)Reaction mechanism

作者：

WANG Yiwen、LIN Lirui、XU Li-Yan、LI En-Min、DONG Geng

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作者单位：

Department of Biochemistry and Molecular Biology,Shantou University Medical College,Shantou 515041,P.R.China

Department of Bioinformatics,Shantou University Medical College,Shantou 515041,P.R.China

Medical Informatics Research Center,Shantou University Medical College,Shantou 515041,P.R.China

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

Cancer Research Center,Shantou University Medical College,Shantou 515041,P.R.China

Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology,Shantou University Medical College,Shantou 515041,P.R.China

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基金：

National Natural Science Foundation of ChinaLi Kashing Foundation,China2020 Li Kashing Foundation Cross-Disciplinary Research Grant,ChinaInnovation Team Grant of Department of Education of Guangdong Provice,ChinaShantou University Medical College(SUMC)Scientific Research Initiation Grant,China

项目编号：

21907063LD01012020LKSFG07B2021KCXTD005510858063

出版年：

2024

DOI：

10.1007/s40242-024-4089-2

高等学校化学研究(英文版)

吉林大学

高等学校化学研究(英文版)

CSTPCD

影响因子：0.871

ISSN：1005-9040

年,卷(期)：2024.40(5)