Metal-dependent inhibition of glyoxalase II: A possible mechanism to regulate the enzyme activity

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.

Graphical abstractGlyoxalase II is a unique enzyme being expressed in different metal forms that are equally active. We report that the enzyme is differentially inhibited in vitro by glutathione (a reaction product) depending on the bound metal ion. Based on the high levels of free glutathione in the cell, this phenomenon could be exploited as a regulatory mechanism of the enzyme activity.Figure optionsDownload full-size imageDownload as PowerPoint slide