Kinetic and docking studies of the interaction of quinones with the quinone reductase active site.
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.
Zhou
Zhigang
Z
Department of Chemistry, Lebanon Valley College, Annville, Pennsylvania 17003, USA.
Fisher
Derek
D
Spidel
Jared
J
Greenfield
Jodi
J
Patson
Brian
B
Fazal
Aleem
A
Wigal
Carl
C
Moe
Owen A
OA
Madura
Jeffry D
JD
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
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