Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular modeling

• DOI: 10.1073/pnas.0701727104
• Publication Date: 2007-04-17T00:54:21Z
• Authors: Bella L. Grigorenko; Alexander V. Rogov; Igor A. Topol; Stanley K. Burt; Hugo M. Martinez; Alexander V. Nemu...
• Keywords: Adenosine triphosphate; Adenosine diphosphate; Bond cleavage

The intrinsic chemical reaction of adenosine triphosphate (ATP) hydrolysis catalyzed by myosin is modeled using a combined quantum mechanics and molecular (QM/MM) methodology that achieves near ab initio representation the entire model. Starting with coordinates derived from heavy atoms crystal structure (Protein Data Bank ID code 1VOM) in which bound to ATP analog ADP.VO(4)(-), minimum-energy path found for transformation + H(2)O --> ADP P(i) characterized two distinct events: (i) low activation-energy cleavage P(gamma) O(betagamma) bond separation gamma-phosphate (ii) formation inorganic phosphate as consequence proton transfers mediated water molecules assisted Glu-459-Arg-238 salt bridge protein. model enzyme-substrate complex features stable hydrogen-bonding network lytic positioned favorably nucleophilic attack transfer stably second water. In addition, has become significantly longer than unbound state thus predisposed cleavage. viewed part overall occurring closed enzyme pocket after tightly before conformational changes preceding release phosphate.