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Acta Naturae. 2010 Jul;2(2):66-71.

Bioinformatic Analysis, Molecular Modeling of Role of Lys65 Residue in Catalytic Triad of D-aminopeptidase from Ochrobactrum anthropi.

Author information

1
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University.

Abstract

A bioinformatic and phylogenetic study has been performed on a family of penicillin-binding proteins including D-aminopeptidases, D-amino acid amidases, DD-carboxypeptidases, and β -lactamases. Significant homology between D-aminopeptidase from Ochrobactrum anthropi and other members of the family has been shown and a number of conserved residues identified as S62, K65, Y153, N155, H287, and G289. Three of those (Ser62, Lys65, and Tyr153) form a catalytic triangle - the proton relay system that activates the generalized nucleophile in the course of catalysis. Molecular modeling has indicated the conserved residue Lys65 to have an unusually low pKa value, which has been confirmed experimentally by a study of the pH-profile of D-aminopeptidase catalytic activity. The resulting data have been used to elucidate the role of Lys65 in the catalytic mechanism of D-aminopeptidase as a general base for proton transfer from catalytic Ser62 to Tyr153, and vice versa, during the formation and hydrolysis of the acyl - enzyme intermediate.

KEYWORDS:

D-aminopeptidase; bioinformatic analysis; catalytic mechanism; penicillin-binding protein family

PMID:
22649642
PMCID:
PMC3347556

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