Proton shuttles and phosphatase activity in soluble epoxide hydrolase.

ABSTRACT: Recently, a novel metal Mg2+-dependent phosphatase activity has been discovered in the N-terminal domain of the soluble epoxide hydrolase (sEH), opening a new branch of fatty acid metabolism and providing an additional site for drug targeting. Importantly, the sEH N-terminal fold belongs to the haloacid dehalogenase (HAD) superfamily, which comprises a vast majority of phosphotransferases. Herein, we present the results of a computational study of the sEH phosphatase activity, which includes classical molecular dynamics (MD) simulations and mixed quantum mechanical/molecular mechanics (QM/MM) calculations. On the basis of experimental results, a two-step mechanism has been proposed and herein investigated: (1) phosphoenzyme intermediate formation and (2) phosphoenzyme intermediate hydrolys

SUBMITTER: De Vivo M 

PROVIDER: S-EPMC2533064 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature