Ribonucleotide Reductase: Recent Advances

Abstract

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides and play an essential role in nucleic acid metabolism in all organisms. RNRs have been divided into three classes. They share a structurally homologous subunit where the reduction occurs, with the chemistry being initiated by thiyl radical‐mediated abstraction of the nucleotide's 3′‐hydrogen atom. The classification of RNRs is based on the different strategies used to generate the transient thiyl radical. The class Ia and Ib RNRs use a diferric‐tyrosyl radical cofactor, the class II RNRs use adenosylcobalamin, and the class III RNRs use a glycyl radical generated by a [4Fe4S] 1+ cluster and S ‐adenosylmethionine. This article focuses on the recent advances in our understanding of the in vitro and in vivo mechanisms of formation of the metallocofactors in the class I RNRs in E. coli and S. cerevisiae . The discovery of a new class of RNR, class Ic, whose active cofactor is proposed to be an Mn IV Fe III cluster, and a summary of recent insights into the chemistry of the novel cofactor are also described. Finally, the current understanding of the unprecedented role of the metallocofactor in radical propagation over 35 Å in the class Ia—and presumably class Ib and Ic—RNRs is presented.

Use of Electron Paramagnetic Resonance To Solve Biochemical Problems

“…Perhaps the most wellcharacterized naturally occurring radicals (tyrosine, tryptophan, and cysteine) are those in the various forms of the ribonucleotide reductase (RNR) family of enzymes. 122 The RNR family of enzymes catalyzes the conversion of ribonucleotides to the deoxyribonucleotides that are used in the synthesis of DNA in every living organism. In this review, we will focus on the class 1 RNR systems that consist of two subunits, R1 and R2.…”