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Identification of the reactive cysteine residues in oligopeptidase B from Trypanosoma brucei
Author(s) -
Morty Rory E.,
Shih Angela Y.,
Fülöp Vilmos,
Andrews Norma W.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.03.014
Subject(s) - trypanosoma brucei , cysteine , oligopeptidase , trypanosoma , identification (biology) , chemistry , biochemistry , biology , enzyme , virology , botany , gene
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.