Ribonucleotide reductase catalytic subunit M1 and regulatory subunit M2 (RNR)

Ribonucleotide reductase (RNR) is a critical enzyme complex that catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides (dNTPs), which are the essential building blocks for DNA replication and repair [1, 8]. The enzyme functions as a heterotetramer composed of two large catalytic subunits (RRM1) and two small regulatory subunits (RRM2) [2, 4]. RRM1 contains the active site and allosteric regulatory sites, while RRM2 houses a stable tyrosyl radical required for catalysis [1, 3]. Because of its central role in cell proliferation, RNR is a well-established therapeutic target in oncology, where its overexpression is frequently associated with poor prognosis and resistance to chemotherapeutic agents like gemcitabine and hydroxyurea [5, 10, 11]. Drugs targeting RNR work by either inhibiting the catalytic activity of RRM1, destroying the tyrosyl radical in RRM2, or preventing the association of the two subunits [1, 2, 6]. Beyond cancer, RNR is also being explored as a target for antiviral therapies due to its role in providing nucleotides for viral genome replication [1, 8].

Other names

Ribonucleoside-diphosphate reductaseRRRRM1RRM2RR1RR2

Inhibition of deoxyribonucleotide synthesis through catalytic site blockade, tyrosyl radical quenching, or disruption of subunit association [1, 2, 3].