1SG0

Crystal structure analysis of QR2 in complex with resveratrol

1SG0 の概要

• エントリーDOI: 10.2210/pdb1sg0/pdb
• 関連するPDBエントリー: 1QR2 2QR2
• 分子名称: NRH dehydrogenase [quinone] 2, ZINC ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: quinone reductase 2, resveratrol, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P16083
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53857.08

構造登録者

Buryanovskyy, L.,Fu, Y.,Boyd, M.,Ma, Y.,Tsieh, T.C.,Wu, J.M.,Zhang, Z. (登録日: 2004-02-22, 公開日: 2005-01-25, 最終更新日: 2024-02-14)

主引用文献

Buryanovskyy, L.,Fu, Y.,Boyd, M.,Ma, Y.,Hsieh, T.C.,Wu, J.M.,Zhang, Z.
Crystal structure of quinone reductase 2 in complex with resveratrol
Biochemistry, 43:11417-11426, 2004

PubMed 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.

PubMed: 15350128
DOI: 10.1021/bi049162o

実験手法

X-RAY DIFFRACTION (1.5 Å)