Inhibition of leucine aminopeptidase by amino acid hydroxamates.

Abstract

Amino acid hydroxamates are strong competitive inhibitors of leucine aminopeptidase from porcine kidney. The side chain specificity for inhibition correlates well with substrate specificity. L-Leucine hydroxamate (Ki = 14 microM) protects the enzyme from inactivation by EDTA and is presumed to be a bidentate ligand of the zinc at the active site. A substituted beta-mercaptoketone which may bind in a similar way is also a potent inhibitor (Ki = approximately 1 microM). The binding of these inhibitors suggests a mechanism for this enzyme in which a zinc-bound hydroxide ion participates in concerted proton-transfer processes, while the coordination and charge field at the zinc atom remain unchanged.