Global and local molecular dynamics of a bacterial carboxylesterase provide insight into its catalytic mechanism.

ABSTRACT: Carboxylesterases (CEs) are ubiquitous enzymes responsible for the detoxification of xenobiotics. In humans, substrates for these enzymes are far-ranging, and include the street drug heroin and the anticancer agent irinotecan. Hence, their ability to bind and metabolize substrates is of broad interest to biomedical science. In this study, we focused our attention on dynamic motions of a CE from B. subtilis (pnbCE), with emphasis on the question of what individual domains of the enzyme might contribute to its catalytic activity. We used a 10 ns all-atom molecular dynamics simulation, normal mode calculations, and enzyme kinetics to understand catalytic consequences of structural changes within this enzyme. Our results shed light on how molecular motions are coupled with catalysis. During mo

SUBMITTER: Yu X 

PROVIDER: S-EPMC3603365 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature