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Identification of the reactive cysteine residues in oligopeptidase B from Trypanosoma brucei
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UNSPECIFIED. (2005) Identification of the reactive cysteine residues in oligopeptidase B from Trypanosoma brucei. FEBS LETTERS, 579 (10). pp. 2191-2196. ISSN 0014-5793
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Official URL: http://dx.doi.org/10.1016/j.febslet.2005.03.014
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-methylmaleimide 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. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
| Journal or Publication Title: | FEBS LETTERS |
| Publisher: | ELSEVIER SCIENCE BV |
| ISSN: | 0014-5793 |
| Date: | 11 April 2005 |
| Volume: | 579 |
| Number: | 10 |
| Number of Pages: | 6 |
| Page Range: | pp. 2191-2196 |
| Identification Number: | 10.1016/j.febslet.2005.03.014 |
| Publication Status: | Published |
| URI: | http://wrap.warwick.ac.uk/id/eprint/7191 |
Data sourced from Thomson Reuters' Web of Knowledge
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