Ribonucleoside diphosphate reductase (RNR)

Ribonucleoside diphosphate reductase (RNR) is an essential enzyme found in all living cells, catalyzing the reduction of ribonucleoside diphosphates (NDPs) to deoxyribonucleoside diphosphates (dNDPs)—the rate-limiting step in the de novo synthesis of deoxyribonucleotides, the precursors for DNA synthesis[1][2][6][8]. This activity is critical for DNA replication and repair, tightly regulated throughout the cell cycle, and necessary for cell proliferation. In humans, RNR is composed of two primary subunits (RRM1 as the large subunit, RRM2 or RRM2B as the small subunit) and its activity is influenced by allosteric regulation, redox state, and cellular demand for dNTPs[1][3]. Because of its central role in nucleic acid metabolism and cell division, RNR is a validated therapeutic target in oncology and anti-infective therapy, with several clinically used inhibitors acting at different mechanistic steps of the enzyme and its regulatory pathways[6][8][3].

Other names

Ribonucleotide reductaseCDP reductaseUDP reductaseADP reductaseNucleoside diphosphate reductaseRibonucleoside 5'-diphosphate reductaseRibonucleotide diphosphate reductase2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductaseRRRNR1RNR2Gene aliases: nrdBnrdFnrdJRRM1RRM2RRM2B

Inhibition of radical formation (e.g., hydroxyurea, triapine) Nucleoside analog competition (e.g., gemcitabine, clofarabine acts as false substrates or active site blockers) Iron/manganese chelation (affecting cofactor assembly or function)