1sg0
From Proteopedia
(New page: 200px<br /> <applet load="1sg0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sg0, resolution 1.50Å" /> '''Crystal structure a...) |
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| - | [[Image:1sg0.gif|left|200px]]<br /> | + | [[Image:1sg0.gif|left|200px]]<br /><applet load="1sg0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1sg0" size=" | + | |
caption="1sg0, resolution 1.50Å" /> | caption="1sg0, resolution 1.50Å" /> | ||
'''Crystal structure analysis of QR2 in complex with resveratrol'''<br /> | '''Crystal structure analysis of QR2 in complex with resveratrol'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Resveratrol has been shown to have chemopreventive, cardioprotective, and | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1SG0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, FAD and STL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http:// | + | 1SG0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=STL:'>STL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SG0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Fu, Y.]] | [[Category: Fu, Y.]] | ||
[[Category: Ma, Y.]] | [[Category: Ma, Y.]] | ||
| - | [[Category: Tsieh, T | + | [[Category: Tsieh, T C.]] |
| - | [[Category: Wu, J | + | [[Category: Wu, J M.]] |
[[Category: Zhang, Z.]] | [[Category: Zhang, Z.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: resveratrol]] | [[Category: resveratrol]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:06 2008'' |
Revision as of 13:01, 21 February 2008
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Crystal structure analysis of QR2 in complex with resveratrol
Overview
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.
About this Structure
1SG0 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as NAD(P)H dehydrogenase (quinone), with EC number 1.6.5.2 Full crystallographic information is available from OCA.
Reference
Crystal structure of quinone reductase 2 in complex with resveratrol., Buryanovskyy L, Fu Y, Boyd M, Ma Y, Hsieh TC, Wu JM, Zhang Z, Biochemistry. 2004 Sep 14;43(36):11417-26. PMID:15350128
Page seeded by OCA on Thu Feb 21 15:01:06 2008
Categories: Homo sapiens | NAD(P)H dehydrogenase (quinone) | Single protein | Boyd, M. | Buryanovskyy, L. | Fu, Y. | Ma, Y. | Tsieh, T C. | Wu, J M. | Zhang, Z. | FAD | STL | ZN | Quinone reductase 2 | Resveratrol
