Thioredoxin and glutaredoxin-mediated redox regulation of ribonucleotide reductase

Figure 2 Subunit organization of ribonucleotide reductase complex. Amino acids are shown with E. coli numbering which are crucial for the radical transfer and ribonucleotide reductase (RNR) catalysis. The R2 subunit contains the iron-oxygen cluster (Fe-O-Fe) which reacts with dioxygen to generate a stable tyrosyl radical in Tyr 122 required for the RNR catalysis. The radical transfer pathway from Tyr 122 to the active-site Cys 439 in R1 subunit involves the network of Asp 84, His 118, Asp 237, Trp 48, Tyr 356 in R2 subunit and Tyr 730, Tyr 731 in R1 subunit[2-5]. The Cys 225, Cys 462, Asn 437 and Glu 441 residues are involved in binding the substrate nucleoside diphosphate (NDP) in R1 subunit. During the catalysis, the disulfide bond between Cys 225 and Cys 462 is reduced by the C-terminal shuttle dithiols[2-5]. The figure is adapted and modified from Holmgren et al[4].