The QM/MM molecular dynamics and free energy simulations of the acylation reaction catalyzed by the serine-carboxyl peptidase kumamolisin-As.

ABSTRACT: Quantum mechanical/molecular mechanical molecular dynamics and free energy simulations are performed to study the acylation reaction catalyzed by kumamolisin-As, a serine-carboxyl peptidase, and to elucidate the catalytic mechanism and the origin of substrate specificity. It is demonstrated that the nucleophilic attack by the serine residue on the substrate may not be the rate-limiting step for the acylation of the GPH*FF substrate. The present study also confirms the earlier suggestions that Asp164 acts as a general acid during the catalysis and that the electrostatic oxyanion hole interactions may not be sufficient to lead a stable tetrahedral intermediate along the reaction pathway. Moreover, Asp164 is found to act as a general base during the formation of the acyl-enzyme from the tetra

SUBMITTER: Xu Q 

PROVIDER: S-EPMC2533263 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature