Selective inhibition of Fe- versus Cu/Zn-superoxide dismutases by 2,3-dihydroxybenzoic acid derivatives.
A series of catechol derivatives were synthesised and tested for their ability to inactivate the iron-containing superoxide dismutase (Fe-SOD) from Escherichia coli and the bovine erythrocytes Cu/Zn-SOD. Incubation of catechols with Fe- or Cu/Zn SODs resulted in a time-dependent loss of enzyme activity with highly selective inhibition for the iron-dependent enzyme. Catechol-induced inactivation of SODs was correlated with the auto-oxidation of the catechol compounds to their corresponding ortho-quinone derivatives, which was found to be non-dependent on the presence of enzymes. Mass electrospray experiments on catechol-incubated Fe-SOD provided evidence for the irreversible nature of the inhibition process, yielding to a complex mixture of modified proteins.
Soulère
Laurent
L
Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, UMR-CNRS 5068-Université Paul Sabatier, Toulouse, France.
Viodé
Cécile
C
Périé
Jacques
J
Hoffmann
Pascal
P
D000818:Animals; D002396:Catechols / Q000737:chemistry; D002417:Cattle; D004912:Erythrocytes / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D062385:Hydroxybenzoates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*
D002396:Catechols; D062385:Hydroxybenzoates; C009135:2,3-dihydroxybenzoic acid; D013482:Superoxide Dismutase