Reaction mechanism of glutamate carboxypeptidase II revealed by mutagenesis, X-ray crystallography and computational methods

Abstract

The peptide hydrolysis by GCPII was investigated in detail by carrying out the kinetic analysis of GCPII(E424A) using N-Ac-Asp-Glu as substrate. The crystal structure of GCPII(E424A) in complex with N-Ac-Asp-Glu was determined at 1.70 A resolution.

The experimental data were then complemented by the QM/MM calculations which provided detailed information concerning the GCPII reaction mechanism.

Keywords

• reaction mechanism
• QM/MM calculations
• glutamate carboxypeptidase II
• X-ray crystallography
• mutant activity