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.
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Authors | Rory E Morty, Angela Y Shih, Vilmos Fülöp, Norma W Andrews |
Journal | FEBS letters
(FEBS Lett)
Vol. 579
Issue 10
Pg. 2191-6
(Apr 11 2005)
ISSN: 0014-5793 [Print] England |
PMID | 15811340
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- Serine Endopeptidases
- oligopeptidase B
- Cysteine
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Topics |
- Amino Acid Sequence
- Animals
- Base Sequence
- Cysteine
(metabolism)
- DNA Primers
- Molecular Sequence Data
- Mutagenesis, Site-Directed
- Sequence Homology, Amino Acid
- Serine Endopeptidases
(chemistry, genetics, metabolism)
- Trypanosoma brucei brucei
(enzymology)
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