Clarification of the mechanism of acylation reaction and origin of substrate specificity of the serine-carboxyl peptidase sedolisin through QM/MM free energy simulations.

ABSTRACT: Quantum mechanical/molecular mechanical (QM/MM) free energy simulations are applied for understanding the mechanism of the acylation reaction catalyzed by sedolisin, a representative serine-carboxyl peptidase, leading to the acyl-enzyme (AE) and first product from the enzyme-catalyzed reaction. One of the interesting questions to be addressed in this work is the origin of the substrate specificity of sedolisin that shows a relatively high activity on the substrates with Glu at P(1) site. It is shown that the bond making and breaking events of the acylation reaction involving a peptide substrate (LLE*FL) seem to be accompanied by local conformational changes, proton transfers as well as the formation of alternative hydrogen bonds. The results of the simulations indicate that the conformatio

SUBMITTER: Xu Q 

PROVIDER: S-EPMC3053426 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature