InterPro domain: IPR039718

Ribonucleotide reductase (RNR, 1.17.4.1 ) [ 1 , 2 ] catalyzes the reductivesynthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. Class I RNRs, found in eukaryotes, bacteria, bacteriophage and viruses, use a diiron-tyrosyl radical, Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Class III RNRs, found in anaerobic bacteria and bacteriophage, use an FeS cluster and S-adenosylmethionine to generate a glycyl radical. Many organisms have more than one class of RNR present in their genomes.

Ribonucleotide reductase is an oligomeric enzyme composed of a large subunit (700 to 1000 residues) and a small subunit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain [ 3 ].

The reduction of ribonucleotides to deoxyribonucleotides involves the transfer of free radicals, the function of each metallocofactor is to generate an active site thiyl radical. This thiyl radical then initiates the nucleotide reduction process by hydrogen atom abstraction from the ribonucleotide [ 4 ]. The radical-based reaction involves five cysteines: two of these are located at adjacent anti-parallel strands in a new type of ten-stranded alpha/beta-barrel; two others reside at the carboxyl end in a flexible arm; and the fifth, in a loop in the centre of the barrel, is positioned to initiate the radical reaction [ 5 ]. There are several regions of similarity in the sequence of the large chain of prokaryotes, eukaryotes and viruses spread across 3 domains: an N-terminal domain common to the mammalian and bacterial enzymes; a C-terminal domain common to the mammalian and viral ribonucleotide reductases; and a central domain common to all three [ 6 ].

1. Structure-function studies of the large subunit of ribonucleotide reductase from Escherichia coli. Biochem. Soc. Trans. 16, 91-4
2. From RNA to DNA, why so many ribonucleotide reductases? Science 260, 1773-7
3. The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer. Nat. Struct. Biol. 9, 293-300
4. Binding of allosteric effectors to ribonucleotide reductase protein R1: reduction of active-site cysteines promotes substrate binding. Structure 5, 1077-92
5. Structure of ribonucleotide reductase protein R1. Nature 370, 533-9