Catalysis by human leukocyte elastase: mechanistic insights into specificity requirements
- 1 March 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 26 (5) , 1301-1305
- https://doi.org/10.1021/bi00379a015
Abstract
Steady-state kinetic parameters were detremined for the human leukocyte elastase catalyzed hydrolysis of a series of peptide-based thiobenzyl esters and p-nitroanilides. The peptide units are Meo-Suc-Val, MeOSuc-Alan-Pro-Val (n = 0-2), and MeOSuc-Alan-Pro-Ala (n = 1 or 2). The results of this study suggest five important mechanistic features for HLE. (1) Few important remote subsite contacts are established in the Michaelis complex. (2) Full recognition and binding of the substrate occurs in the transition state for acylation. (3) The P3.sbd.S3 interaction is critical during acylation. (4) Subsite contacts are unimportant in deacylation. (4) P1 specificity is regulated by peptide length. An important steady-state kinetic consequence of this specificity is that the rate-limiting step of kc for p-nitroanilide hydrolysis changes from acylation to deacylation as the peptide chain is lengthened.This publication has 10 references indexed in Scilit:
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