Biochimica et Biophysica Acta 1985-07-01

Mechanistic implications of the inhibition of peptidases by amino aldehydes and bestatin.

L Frick, R Wolfenden

Index: Biochim. Biophys. Acta 829(3) , 311-8, (1985)

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Abstract

alpha-Amino aldehydes and bestatin are found to be effective inhibitors of a cytosolic dipeptidase (rat testicular peptidase C), and a cytosolic tripeptidase (rat kidney peptidase B, EC 3.4.11.4), as well as cytosolic leucine aminopeptidase (pig kidney peptidase S, EC 3.4.11.1). Aldehyde hydrates and bestatin share a resemblance to intermediates that might be formed during direct attack by water on peptide substrates, affording a possible explanation for their tight binding. Alternatively, inhibitors of both kinds might form derivatives of an active site nucleophile, resembling intermediates in a double-displacement mechanism. Exchange experiments with H218O suggest that bestatin is bound intact by leucine aminopeptidase, lending support to the first of these two mechanisms.