Crystal structure of quinone reductase 2 in complex with resveratrol.

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Buryanovskyy L, Fu Y, Boyd M, Ma Y, Hsieh TC, Wu JM, Zhang Z

Crystal structure of quinone reductase 2 in complex with resveratrol.

Biochemistry. 2004 Sep 14;43(36):11417-26.

PubMed ID

15350128 [ View in PubMed

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Abstract

Resveratrol has been shown to have chemopreventive, cardioprotective, and antiaging properties. Here, we report that resveratrol is a potent inhibitor of quinone reductase 2 (QR2) activity in vitro with a dissociation constant of 35 nM and show that it specifically binds to the deep active-site cleft of QR2 using high-resolution structural analysis. All three resveratrol hydroxyl groups form hydrogen bonds with amino acids from QR2, anchoring a flat resveratrol molecule in parallel with the isoalloxazine ring of FAD. The unique active-site pocket in QR2 could potentially bind other natural polyphenols such as flavonoids, as proven by the high affinity exhibited by quercetin toward QR2. K562 cells with QR2 expression suppressed by RNAi showed similar properties as resveratrol-treated cells in their resistance to quinone toxicity. Furthermore, the QR2 knockdown K562 cells exhibit increased antioxidant and detoxification enzyme expression and reduced proliferation rates. These observations could imply that the chemopreventive and cardioprotective properties of resveratrol are possibly the results of QR2 activity inhibition, which in turn, up-regulates the expression of cellular antioxidant enzymes and cellular resistance to oxidative stress.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Quercetin	Ribosyldihydronicotinamide dehydrogenase [quinone]	Protein	Humans	Unknown	Inhibitor	Details
Resveratrol	Ribosyldihydronicotinamide dehydrogenase [quinone]	Protein	Humans	Unknown	Not Available	Details

Polypeptides

Name	UniProt ID
Ribosyldihydronicotinamide dehydrogenase [quinone]	P16083	Details