Ribonucleoside-diphosphate reductase subunit M2 tyrosyl radical center (RRM2 tyrosyl radical)

The Ribonucleotide reductase class I, M2 subunit (RRM2) tyrosyl radical center is a vital catalytic component of the enzyme responsible for converting ribonucleotides into deoxyribonucleotides (UniProt: P31350). This center consists of a stable tyrosyl radical generated and maintained by a non-heme di-iron cofactor within the RRM2 subunit. During catalysis, the radical is shuttled to the RRM1 subunit to initiate the reduction process, making it essential for DNA synthesis and repair (PMID: 15591231). Due to its role in providing the building blocks for DNA, RRM2 is often upregulated in rapidly dividing cancer cells, correlating with poor prognosis and treatment resistance. Therapeutic strategies targeting this site typically involve radical scavengers, such as hydroxyurea, or iron chelators that disrupt the di-iron center (PMID: 21548802). By quenching the tyrosyl radical, these agents inhibit the production of dNTPs, leading to S-phase arrest and apoptosis in malignant cells.

Other names

Ribonucleoside-diphosphate reductase subunit M2RRM2Ribonucleotide reductase M2 subunitTyrosyl radical centerR2 subunit

The drugs act as radical scavengers or iron chelators that quench the essential tyrosyl radical within the M2 subunit, thereby halting the conversion of ribonucleotides to deoxyribonucleotides and inhibiting DNA synthesis (PMID: 21548802, StatPearls: Hydroxyurea).