naphthoquinones and isoalloxazine

NAD(P)H/quinone acceptor oxidoreductase type 1 (QR1) protects cells from cytotoxic and neoplastic effects of quinones though two-electron reduction. Kinetic experiments, docking, and binding affinity calculations were performed on a series of structurally varied quinone substrates. A good correlation between calculated and measured binding affinities from kinetic determinations was obtained. The experimental and theoretical studies independently support a model in which quinones (with one to three fused aromatic rings) bind in the QR1 active site utilizing a pi-stacking interaction with the isoalloxazine ring of the FAD cofactor.

Topics: Animals; Anthraquinones; Benzoquinones; Binding Sites; Flavins; Humans; Kinetics; Models, Chemical; Models, Molecular; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Rats; Structure-Activity Relationship; Substrate Specificity; Thermodynamics; Tyrosine