NQO1 Holo Form

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NQO1 (NQO1, EC 1.6.5.2) functions as a dimeric, two-domain FAD-dependent enzyme that catalyzes the two-electron reduction of quinones and related substrates through an enzyme-substituted mechanism in which NAD(P)H enters the active site, reduces the FAD, and exits as the oxidized form, allowing subsequent substrate binding and reduction by the FADH2. Primarily, NQO1 prevents the formation of reactive semiquinones, maintains antioxidants such as α-tocopherol and ubiquinone in their reduced state, and activates some anticancer bioreductive drugs. Additionally, NQO1 interacts with tumour suppressors like p53 and p73, stabilizing them against proteasomal degradation while its interaction with the 20S proteasome prevents the degradation of various proteins with intrinsically disordered regions, including several cell cycle regulators, tumor suppressors, and apoptotic proteins. The study of NQO1 polymorphisms is particularly interesting due to its elevated expression in several types of cancer.