Key result
Molecular orbital modeling reveals nonbridging γ-phosphoryl oxygen atoms as the myosin ATP hydrolysis site.
Why the study?
The reaction site of ATP hydrolysis in the myosin motor domain and the role of hydrolytic water were not fully elucidated at the molecular orbital level.
Molecular orbital modeling identifies the nonbridging γ-phosphoryl oxygen atoms as the reaction site for ATP hydrolysis in the myosin motor domain.
Model of MgATP-myosin interaction aids mechanistic hypotheses; leaves open validation in cardiac muscle systems.
We constructed a model structure of Mg−adenosine triphosphate (MgATP) and the surrounding portion of myosin by using the X-ray crystal structure of the myosin motor domain bound to the stable MgATP analogue, MgADP−BeF x, and by adding hydrogen atoms and replacing beryllium with phosphorus and fluorine with oxygen. The positions of the hydrogen atoms were determined by optimization using the semiempirical molecular orbital program MOPAC 97. Analysis of the electronic states of the model structure revealed that the highest occupied molecular orbitals (HOMO) indicate that the reaction site of the ATP hydrolysis is the nonbridging γ-phosphoryl oxygen atoms and confirmed that H 2 O(1181) is the hydrolytic water. Thus, hypothetical mechanisms of the initial phase of the hydrolysis are proposed.
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Kagawa et al. (1999) studied this question. Molecular orbital modeling of MgATP and myosin motor domain was evaluated on Reaction site of ATP hydrolysis. Molecular orbital modeling of MgATP and the myosin motor domain revealed that the highest occupied molecular orbitals indicate the nonbridging γ-phosphoryl oxygen atoms as the ATP hydrolysis site.
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