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

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+P_i. 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 P _γ—O_S of ATP and bond formation between oxygen of the lytic water and P _γ atoms 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 H₂P _γO₄ ⁻ 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.

Keywords

Actin / Adenosine triphosphate (ATP) hydrolysis / Quantum mechanical and molecular mechanics (QM/MM) / Reaction mechanism

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