Regulation and Plasticity of Catalysis in Enzymes: Insights from Analysis of Mechanochemical Coupling in Myosin.

ABSTRACT: The mechanism of ATP hydrolysis in the myosin motor domain is analyzed using a combination of DFTB3/CHARMM simulations and enhanced sampling techniques. The motor domain is modeled in the pre-powerstroke state, in the post-rigor state, and as a hybrid based on the post-rigor state with a closed nucleotide-binding pocket. The ATP hydrolysis activity is found to depend on the positioning of nearby water molecules, and a network of polar residues facilitates proton transfer and charge redistribution during hydrolysis. Comparison of the observed hydrolysis pathways and the corresponding free energy profiles leads to detailed models for the mechanism of ATP hydrolysis in the pre-powerstroke state and proposes factors that regulate the hydrolysis activity in different conformational states. In t

SUBMITTER: Lu X 

PROVIDER: S-EPMC5705175 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature