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 Lettjournal_title
FEBS lettersauthors
Morty RE,Shih AY,Fülöp V,Andrews NWdoi
10.1016/j.febslet.2005.03.014keywords:
subject
Has Abstractpub_date
2005-04-11 00:00:00pages
2191-6issue
10eissn
0014-5793issn
1873-3468pii
S0014-5793(05)00336-4journal_volume
579pub_type
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