Abstract
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.
基金项目
National Natural Science Foundation of China(21907063)
Li Kashing Foundation,China(LD0101)
2020 Li Kashing Foundation Cross-Disciplinary Research Grant,China(2020LKSFG07B)
Innovation Team Grant of Department of Education of Guangdong Provice,China(2021KCXTD005)
Shantou University Medical College(SUMC)Scientific Research Initiation Grant,China(510858063)
NETL
NSTL
万方数据