Citation

Wakselman M, Joyeau R, Kobaiter R, Boggetto N, Vergely I, Maillard J, Okochi V, Montagne JJ, Reboud-Ravaux M. FEBS Lett. 1991; 282(2): 377-381.

Copyright

(Copyright © 1991, Federation of European Biochemical Societies, Publisher Elsevier Publishing)

DOI

10.1016/0014-5793(91)80517-7

PMID

2037052

Abstract

A functionalized N-aryl azetidinone has been shown to inactivate human leukocyte elastase (HLE) and porcine pancreatic elastase (PPE) by an enzyme-mediated process. The inactivation is characterized by the following kinetic constants at pH 8.0 and 37 degrees C: kinact = 0.035 s-1, KI = 1.2 x 10(-4) M for HLE, 0.08 s-1 and 2.7 x 10(-4) M for PPE, respectively. Two parent molecules devoid of the latent leaving group failed to inactivate HLE and PPE and behaved as substrates of these enzymes. A suicide mechanism is postulated involving the formation of an acyl-enzyme and the simultaneous unmasking of a latent quinonimmonium methide ion which irreversibly reacts with an active site nucleophile. Moreover, the inhibitor is still effective at inhibiting elastase preabsorbed onto elastin.

Language: en

Keywords

Animals; Azetidines; Binding Sites; Elastin; Kinetics; Neutrophils; Pancreas; Pancreatic Elastase; Swine