Identification of the reactive cysteine residues in oligopeptidase B from Trypanosoma brucei.

Abstract:

:Oligopeptidase B (OpdB) from Trypanosoma brucei is a candidate therapeutic target in African trypanosomiasis. OpdB is an atypical serine peptidase, since activity is inhibited by thiol-blocking reagents and enhanced by reducing agents. We have identified C256 as the reactive cysteine residue that mediates OpdB inhibition by N-ethylmaleimide and iodoacetic acid. Modeling studies suggest that C256 adducts occlude the P(1) substrate-binding site, preventing substrate binding. We further demonstrate that C559 and C597 are responsible for the thiol-enhancement of OpdB activity. These studies may facilitate the development of specific OpdB inhibitors with therapeutic potential, by exploiting these unique properties of this enzyme.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Morty RE,Shih AY,Fülöp V,Andrews NW

doi

10.1016/j.febslet.2005.03.014

keywords:

subject

Has Abstract

pub_date

2005-04-11 00:00:00

pages

2191-6

issue

10

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)00336-4

journal_volume

579

pub_type

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