Ribosyldihydronicotinamide dehydrogenase [quinone] (NQO2) (NQO2)

Ribosyldihydronicotinamide dehydrogenase [quinone], commonly known as NQO2, is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones and related compounds (UniProt: P16083). Unlike its relative NQO1, which uses NADH or NADPH, NQO2 specifically utilizes N-ribosyldihydronicotinamide (NRH) as an electron donor (PubMed: 15548212). This enzyme is also identified as the MT3 melatonin binding site, suggesting a unique link between circadian rhythms and cellular redox homeostasis (PubMed: 10804003). NQO2 is involved in the detoxification of xenobiotics and the regulation of oxidative stress, but it can also activate certain pro-carcinogens or prodrugs into reactive species (PubMed: 22433004). Its expression is often altered in various cancers and neurodegenerative conditions, making it a target of interest for both chemoprevention and therapeutic intervention (PubMed: 25660580). Small molecules like resveratrol and melatonin act as potent inhibitors, while specific quinone-based compounds are explored as NQO2-activated prodrugs in oncology (PubMed: 18484711). Understanding the balance between its protective detoxification roles and its potential to generate reactive metabolites is crucial for drug development targeting this enzyme.

Other names

Quinone reductase 2QR2NRH:quinone oxidoreductase 2N-ribosyldihydronicotinamide:quinone oxidoreductase 2Melatonin receptor type 3MT3

NQO2 functions as a flavoprotein enzyme that catalyzes the two-electron reduction of quinones and their derivatives, utilizing N-ribosyldihydronicotinamide (NRH) as a co-factor (UniProt: P16083). Drugs can act as competitive inhibitors, such as melatonin and resveratrol, which bind to the active site and prevent substrate reduction (PubMed: 10804003). Alternatively, NQO2 can act as an activating enzyme for prodrugs, converting relatively non-toxic quinone derivatives into potent cytotoxic agents through reduction (PubMed: 22433004).