title: Metal-dependent inhibition of glyoxalase II: a possible mechanism to regulate the enzyme activity.
abstract: Glyoxalase II (GLX2, EC 3.1.2.6., hydroxyacylglutathione hydrolase) is a metalloenzyme involved in crucial detoxification pathways. Different studies have failed in identifying the native metal ion of this enzyme, which is expressed with iron, zinc and/or manganese. Here we report that GloB, the GLX2 from Salmonella typhimurium, is differentially inhibited by glutathione (a reaction product) depending on the bound metal ion, and we provide a structural model for this inhibition mode. This metal-dependent inhibition was shown to occur in metal-enriched forms of the enzyme, complementing the spectroscopic data. Based on the high levels of free glutathione in the cell, we suggest that the expression of the different metal forms of GLX2 during Salmonella infection could be exploited as a mechanism to regulate the enzyme activity.
authors.affiliation: IBR (Instituto de Biología Molecular y Celular de Rosario), Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. campos@cefobi-conicet.gov.ar
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Campos-Bermudez
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Morán-Barrio
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Costa-Filho
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Vila
mesh_terms: D005978:Glutathione / Q000494:pharmacology; D007501:Iron; D007700:Kinetics; D008345:Manganese; D008667:Metalloproteins / Q000037:antagonists & inhibitors; D019216:Metals, Heavy / Q000494:pharmacology*; D012480:Salmonella Infections; D012486:Salmonella typhimurium; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors*; D015032:Zinc; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D005978:Glutathione; D007501:Iron; D008345:Manganese; D008667:Metalloproteins; D019216:Metals, Heavy; D013869:Thiolester Hydrolases; D015032:Zinc; D000099301:Hydroxyacylglutathione Hydrolase
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