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 s...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.展开更多
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).
文摘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.
