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PDBsum entry 1sg0
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Oxidoreductase
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PDB id
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1sg0
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References listed in PDB file
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Key reference
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Title
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Crystal structure of quinone reductase 2 in complex with resveratrol.
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Authors
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L.Buryanovskyy,
Y.Fu,
M.Boyd,
Y.Ma,
T.C.Hsieh,
J.M.Wu,
Z.Zhang.
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Ref.
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Biochemistry, 2004,
43,
11417-11426.
[DOI no: ]
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PubMed id
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Abstract
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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.
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