Interaction of the (2S,3S)-isomer of bestatin with yeast aminopeptidase I. Kinetic and binding studies.

Inhibition of yeast aminopeptidase I by N-[(2S,3S)-3-amino-2-hydroxyl-1-oxo-4-phenylbutyl]-L-leucine [(2S,3S)-Ahp-Leu];a stereoisomer of natural bestatin, is a slow process with half-times in the minute range. Action of the inhibitor is non-competitive with respect to the substrate. Up to 1 mol of (2S,3S)-Ahp-Leu is bound per mol of enzyme subunit. Inhibitor binding does not interfere with binding of essential metal ions but completely suppresses allosteric activation by chloride and high Zn(II)-concentrations. These and other findings suggest that (2S,3S)-Ahp-Leu inhibits aminopeptidase I by stabilizing a weakly active enzyme conformation.