Thioredoxin and glutaredoxin-mediated redox regulation of ribonucleotide reductase

Figure 1 Crystal structure of Class I aerobic ribonucleotide reductase complex (A), and proposed reaction mechanism of ribonucleotide reductase catalysis (B). A: This is based on the crystal structures of the R1 and R2 proteins (Protein Data Bank ID: 1RLR and 1RIB). The figure shows the presence of substrate in R1 subunit and dinuclear iron center in R2 subunit. The ribonucleotide reductase complex (RNR) complex is a tetramer with the dimer of R1 subunit and the dimer of R2 subunit. The allosteric regulatory domain of R1 subunit (ATP-cone) binds either ATP or dATP to regulate the enzymatic activity (adapted from Logan et al[9]); B: The figure describes the reduction of nucleoside diphosphate (NDP) to deoxyribonucleoside diphosphates (dNDP) by class I RNR (E. coli). The reduction is initiated by a thiyl radical (Cys 439) by abstracting the 3′-hydrogen from the NDP. A water molecule is lost and the two cysteines (Cys 225 and Cys 462) then deliver the required reducing equivalents, generating a 3′-ketodeoxynucleotide which is subsequently reduced to give dNDP (adapted from Holmgren et al[4]).