Structural insights into the initiation of free radical formation in the Class Ib ribonucleotide reductases

Abstract

Class I ribonucleotide reductases consisting of R1 and R2 subunits convert ribonucleoside diphosphates to deoxyribonucleoside diphosphates involving an intricate free radical mechanism. The generation of free radicals in the Class Ib ribonucleotide reductases is mediated by reaction involving di-manganese ions in the R2 subunits and is externally assisted by flavodoxin-like NrdI subunit. This is unlike Class Ia ribonucleotide reductases, where the free radical generation is initiated at its di-iron centre in the R2 subunits with no external support from another subunit. Despite much work on the R2 subunits of Class Ib ribonucleotide reductases, also referred as NrdF, and its partner NrdI, the structural details of free radical generation remain largely unknown. In this study we have determined the crystal structures of Mycobacterial NrdI in oxidized and reduced forms, and similarly those of NrdF2: