Interaction with substrate sensitises caspase-3 to inactivation by hydrogen peroxide

Détails

ID Serval
serval:BIB_73EED3EED349
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Interaction with substrate sensitises caspase-3 to inactivation by hydrogen peroxide
Périodique
FEBS Letters
Auteur(s)
Hampton  M. B., Stamenkovic  I., Winterbourn  C. C.
ISSN
0014-5793 (Print)
Statut éditorial
Publié
Date de publication
2002
Volume
517
Numéro
1-3
Pages
229-232
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Résumé
Caspases have an active site cysteine whose oxidation blocks catalytic activity. Caspase activity, measured in lysates of apoptotic cells, was inhibited by H2O2 with an IC50 of 7 microM. Recombinant caspase-3 was directly inhibited by H2O2, with an estimated second-order rate constant of 750 M-1 s-1. These values were determined when H2O2 was added while the caspases were cleaving a peptide substrate. There was a 40-fold decrease in sensitivity to inactivation if the substrate was absent at the time of H2O2 addition. These results rationalise conflicting reports of the sensitivity of caspase-3 to H2O2, and identify a novel mechanism for sensitising a thiol enzyme to oxidative inactivation
Mots-clé
Binding Sites/Caspase 3/Caspases/antagonists & inhibitors/metabolism/Catalysis/drug effects/Cysteine/Humans/Hydrogen Peroxide/pharmacology/Inhibitory Concentration 50/Jurkat Cells/Oligopeptides/Oxidation-Reduction/Substrate Specificity
Pubmed
Web of science
Création de la notice
29/01/2008 19:33
Dernière modification de la notice
03/03/2018 18:20
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