nrdD

nrdD is the gene encoding the catalytic subunit of the class III anaerobic ribonucleotide reductase (RNR) in bacteria and some archaea. The enzyme catalyzes the reduction of ribonucleotides to deoxyribonucleotides under strictly anaerobic conditions, providing the building blocks for DNA synthesis when oxygen-dependent ribonucleotide reductases are inactive. The activity of NrdD depends on the radical-generating activase NrdG, which uses S-adenosylmethionine to generate a glycyl radical on a conserved glycine residue of NrdD; this radical initiates substrate conversion. Thus, the NrdD–NrdG pair constitutes a two-component anaerobic RNR system. Class III RNRs are inhibited by oxygen; exposure to oxygen can inactivate the glycyl radical or cause enzyme damage.

Genomic context often places nrdD adjacent to nrdG, and many genomes also encode the transcription regulator NrdR, a zinc-finger protein that modulates the expression of ribonucleotide reductase genes in response to nucleotide pools. NrdD proteins are typically large cytosolic enzymes (~700–900 amino acids) containing the catalytic site and a conserved glycyl radical motif.

Physiological role: in anaerobic habitats or during anaerobic growth, nrdD provides deoxyribonucleotides for DNA replication and repair. In facultative anaerobes, expression of nrdD is upregulated under oxygen limitation.

Distribution: widely distributed among anaerobic bacteria and some archaea; often found in environments such as soils, sediments, the gastrointestinal tract, and in certain pathogens where low-oxygen niches exist.

See also: ribonucleotide reductase, class III; nrdG; nrdR.