Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2053422 | FEBS Letters | 2005 | 6 Pages |
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 P1 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.
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Authors
Rory E. Morty, Angela Y. Shih, Vilmos Fülöp, Norma W. Andrews,