title: Kinetic and docking studies of the interaction of quinones with the quinone reductase active site.
abstract: 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.
authors.affiliation: Department of Chemistry, Lebanon Valley College, Annville, Pennsylvania 17003, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Derek
authors.initials: D
authors.lastname: Fisher
authors.forename: Jared
authors.initials: J
authors.lastname: Spidel
authors.forename: Jodi
authors.initials: J
authors.lastname: Greenfield
authors.forename: Brian
authors.initials: B
authors.lastname: Patson
authors.forename: Aleem
authors.initials: A
authors.lastname: Fazal
authors.forename: Carl
authors.initials: C
authors.lastname: Wigal
authors.forename: Owen A
authors.initials: OA
authors.lastname: Moe
authors.forename: Jeffry D
authors.initials: JD
authors.lastname: Madura
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry*; D001665:Binding Sites; D005415:Flavins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D009285:Naphthoquinones / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000880:Anthraquinones; D016227:Benzoquinones; D005415:Flavins; D009285:Naphthoquinones; C042834:9,10-anthraquinone; C004532:quinone; D014443:Tyrosine; C008173:isoalloxazine; D016660:NAD(P)H Dehydrogenase (Quinone); C035342:1,4-naphthoquinone; C034257:duroquinone