Thioredoxin and glutaredoxin-mediated redox regulation of ribonucleotide reductase

Figure 3 The mechanistic model for the role of thioredoxins and glutaredoxins for the ribonucleotide reductase catalysis. After the completion of one turnover cycle of ribonucleotide reductase (RNR) catalysis, a disulfide bond is formed between the conserved cysteine pair at the active site (shown in the circle). Shuttle dithiol function present at the C-terminal CXXC motif of the neighboring subunit reduces the disulfide bond through disulfide-exchange. Then, the resulting disulfide bond at the C-terminal tail is reduced by the thioredoxin/glutaredoxin (Trx/Grx) systems resulting in an active R1 to continue the next cycle of RNR catalysis. The Grx system can also reduce the C-terminal thiols by the glutathionylation mechanism[4,25,26]. For simplicity, only the reduction of active site of one subunit by the C-terminal shuttle dithiols of the neighboring subunit is shown in the diagram. The figure is adapted and modified from Holmgren et al[4].