Ribosyldihydronicotinamide dehydrogenase [quinone] (Quinone reductase 2) (NQO2)

Ribosyldihydronicotinamide dehydrogenase [quinone], commonly known as Quinone reductase 2 (NQO2), is a cytosolic flavoenzyme that has been identified as the primary high-affinity binding site for resveratrol in HT29 colon cancer cells (Delmas, D., et al., 2003, PubMed: 12843170). Unlike the related NQO1, NQO2 specifically utilizes dihydronicotinamide riboside (NRH) as an electron donor to catalyze the two-electron reduction of quinones into hydroquinones, a process that typically bypasses the production of semi-quinone radicals and reactive oxygen species (UniProtKB, P16083). In the context of oncology, NQO2 is involved in the regulation of the cell cycle and the stabilization of the tumor suppressor protein p53; its inhibition by resveratrol is a key mechanism through which the polyphenol exerts anti-proliferative and pro-apoptotic effects in colorectal cancer models (Bury, M., et al., 2005, PubMed: 15955559). Beyond its role in cancer, NQO2 is also recognized as the MT3 binding site for melatonin, suggesting it plays a broader role in metabolic and neurological signaling. The interaction between resveratrol and NQO2 highlights the enzyme's potential as a therapeutic target for chemoprevention and the treatment of redox-related pathologies.

Other names

Quinone reductase 2QR2NRH:quinone oxidoreductase 2Melatonin receptor type 3MT3N-ribosyl-nicotinamide:quinone oxidoreductase

Resveratrol acts as a potent competitive inhibitor of NQO2 by binding to the catalytic site, which prevents the enzyme from utilizing dihydronicotinamide riboside (NRH) to reduce quinones, thereby modulating cellular redox status and inducing p53-dependent pathways (Calamini, B., et al., 2010, PubMed: 20415611).