Fig. 1.

Catalytic mechanism of class I glutaredoxins. A) Dithiol mechanism for the reversible reduction of nonglutathione disulfides. B) Monothiol mechanism for the reversible reduction of glutathionylated substrates. C) Top view of a model of monothiol class I ScGrx7 with glutathione (GS) at the 1st glutathione-interaction site (left). Residues that were shown to contribute to the 1st glutathione-interaction site are highlighted in salmon (middle). Residues and GS that were shown to form the or to recruit GSH to the transient 2nd glutathione-interaction site are shown in blue (right). D) Schematic representation of a side view of the two distinct glutathione-interaction sites that bind or rather encounter the two glutathione moieties during both half-reactions. E) The dithiol mechanism could resolve sterically blocked enzyme intermediates and reintroduce dead-end species in the catalytic cycle. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)