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PDBsum entry 1sg0
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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1sg0

 

 

 

 

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Contents
Protein chain
230 a.a. *
Ligands
FAD ×2
STL ×2
Metals
_ZN ×2
Waters ×353
* Residue conservation analysis
PDB id:
1sg0
Name: Oxidoreductase
Title: Crystal structure analysis of qr2 in complex with resveratrol
Structure: Nrh dehydrogenase [quinone] 2. Chain: a, b. Synonym: quinone reductase 2, qr2, nrh:quinone oxidoreductase 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nqo2, nmor2, bc006096. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.50Å     R-factor:   0.214     R-free:   0.234
Authors: L.Buryanovskyy,Y.Fu,M.Boyd,Y.Ma,T.C.Tsieh,J.M.Wu,Z.Zhang
Key ref:
L.Buryanovskyy et al. (2004). Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry, 43, 11417-11426. PubMed id: 15350128 DOI: 10.1021/bi049162o
Date:
22-Feb-04     Release date:   25-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16083  (NQO2_HUMAN) -  Ribosyldihydronicotinamide dehydrogenase [quinone] from Homo sapiens
Seq:
Struc: 		231 a.a.
230 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.10.5.1  - ribosyldihydronicotinamide dehydrogenase (quinone).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide + a quinone + H+ = beta-nicotinamide D-riboside + a quinol
1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide
 + quinone
 + H(+)
 = beta-nicotinamide D-riboside
 + quinol
      Cofactor: FAD; Zn(2+)
FAD
Bound ligand (Het Group name = FAD) corresponds exactly 		Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi049162o Biochemistry 43:11417-11426 (2004)
PubMed id: 15350128  
 
 
Crystal structure of quinone reductase 2 in complex with resveratrol.
L.Buryanovskyy, Y.Fu, M.Boyd, Y.Ma, T.C.Hsieh, J.M.Wu, Z.Zhang.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21440448 B.F.Ruan, X.Lu, J.F.Tang, Y.Wei, X.L.Wang, Y.B.Zhang, L.S.Wang, and H.L.Zhu (2011).
Synthesis, biological evaluation, and molecular docking studies of resveratrol derivatives possessing chalcone moiety as potential antitubulin agents.
  Bioorg Med Chem, 19, 2688-2695.  
21261650 J.M.Pezzuto (2011).
The phenomenon of resveratrol: redefining the virtues of promiscuity.
  Ann N Y Acad Sci, 1215, 123-130.  
21261637 J.M.Wu, and T.C.Hsieh (2011).
Resveratrol: a cardioprotective substance.
  Ann N Y Acad Sci, 1215, 16-21.  
20566882 A.A.Khutornenko, V.V.Roudko, B.V.Chernyak, A.B.Vartapetian, P.M.Chumakov, and A.G.Evstafieva (2010).
Pyrimidine biosynthesis links mitochondrial respiration to the p53 pathway.
  Proc Natl Acad Sci U S A, 107, 12828-12833.  
20450491 B.Calamini, K.Ratia, M.G.Malkowski, M.Cuendet, J.M.Pezzuto, B.D.Santarsiero, and A.D.Mesecar (2010).
Pleiotropic mechanisms facilitated by resveratrol and its metabolites.
  Biochem J, 429, 273-282.  
20633117 G.F.Oxenkrug, S.O.Bachurin, I.V.Prakhie, and N.S.Zefirov (2010).
Quinone reductase 2 and antidepressant effect of melatonin derivatives.
  Ann N Y Acad Sci, 1199, 121-124.  
20219519 J.A.Baur (2010).
Resveratrol, sirtuins, and the promise of a DR mimetic.
  Mech Ageing Dev, 131, 261-269.  
20100622 J.H.Yang, T.P.Kondratyuk, L.E.Marler, X.Qiu, Y.Choi, H.Cao, R.Yu, M.Sturdy, S.Pegan, Y.Liu, L.Q.Wang, A.D.Mesecar, R.B.Van Breemen, J.M.Pezzuto, H.H.Fong, Y.G.Chen, and H.J.Zhang (2010).
Isolation and evaluation of kaempferol glycosides from the fern Neocheiropteris palmatopedata.
  Phytochemistry, 71, 641-647.  
20560755 R.H.Singleton, H.Q.Yan, W.Fellows-Mayle, and C.E.Dixon (2010).
Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury.
  J Neurotrauma, 27, 1091-1099.  
  20623546 T.C.Hsieh, and J.M.Wu (2010).
Resveratrol: Biological and pharmaceutical properties as anticancer molecule.
  Biofactors, 36, 360-369.  
19265439 A.Maiti, P.V.Reddy, M.Sturdy, L.Marler, S.D.Pegan, A.D.Mesecar, J.M.Pezzuto, and M.Cushman (2009).
Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities.
  J Med Chem, 52, 1873-1884.
PDB codes: 3g5m 3gam
19236722 J.A.Winger, O.Hantschel, G.Superti-Furga, and J.Kuriyan (2009).
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).
  BMC Struct Biol, 9, 7.
PDB code: 3fw1
  19625701 J.M.Pezzuto, V.Venkatasubramanian, M.Hamad, and K.R.Morris (2009).
Unraveling the relationship between grapes and health.
  J Nutr, 139, 1783S-1787S.  
19432534 S.Pervaiz, and A.L.Holme (2009).
Resveratrol: its biologic targets and functional activity.
  Antioxid Redox Signal, 11, 2851-2897.  
18794327 C.Yan, J.K.Kepa, D.Siegel, I.J.Stratford, and D.Ross (2008).
Dissecting the role of multiple reductases in bioactivation and cytotoxicity of the antitumor agent 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone (RH1).
  Mol Pharmacol, 74, 1657-1665.  
18826489 J.A.Boutin, E.Marcheteau, P.Hennig, N.Moulharat, S.Berger, P.Delagrange, J.P.Bouchet, and G.Ferry (2008).
MT3/QR2 melatonin binding site does not use melatonin as a substrate or a co-substrate.
  J Pineal Res, 45, 524-531.  
17512093 J.Brouillette, and R.Quirion (2008).
Transthyretin: a key gene involved in the maintenance of memory capacities during aging.
  Neurobiol Aging, 29, 1721-1732.  
18421779 L.Pirola, and S.Fröjdö (2008).
Resveratrol: one molecule, many targets.
  IUBMB Life, 60, 323-332.  
18602018 P.L.Toogood (2008).
Mitochondrial drugs.
  Curr Opin Chem Biol, 12, 457-463.  
18493248 R.Jockers, P.Maurice, J.A.Boutin, and P.Delagrange (2008).
Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?
  Br J Pharmacol, 154, 1182-1195.  
  18383821 T.C.Hsieh, Z.Wang, H.Deng, and J.M.Wu (2008).
Identification of glutathione sulfotransferase-pi (GSTP1) as a new resveratrol targeting protein (RTP) and studies of resveratrol-responsive protein changes by resveratrol affinity chromatography.
  Anticancer Res, 28, 29-36.  
18579530 Y.Fu, L.Buryanovskyy, and Z.Zhang (2008).
Quinone reductase 2 is a catechol quinone reductase.
  J Biol Chem, 283, 23829-23835.  
17698806 J.R.Gledhill, M.G.Montgomery, A.G.Leslie, and J.E.Walker (2007).
Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols.
  Proc Natl Acad Sci U S A, 104, 13632-13637.
PDB codes: 2jiz 2jj1 2jj2
17720881 U.Rix, O.Hantschel, G.Dürnberger, L.L.Remsing Rix, M.Planyavsky, N.V.Fernbach, I.Kaupe, K.L.Bennett, P.Valent, J.Colinge, T.Köcher, and G.Superti-Furga (2007).
Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets.
  Blood, 110, 4055-4063.  
17261084 Y.Hu, S.Rahlfs, V.Mersch-Sundermann, and K.Becker (2007).
Resveratrol modulates mRNA transcripts of genes related to redox metabolism and cell proliferation in non-small-cell lung carcinoma cells.
  Biol Chem, 388, 207-219.  
16732220 J.A.Baur, and D.A.Sinclair (2006).
Therapeutic potential of resveratrol: the in vivo evidence.
  Nat Rev Drug Discov, 5, 493-506.  
16217127 A.Slominski, T.W.Fischer, M.A.Zmijewski, J.Wortsman, I.Semak, B.Zbytek, R.M.Slominski, and D.J.Tobin (2005).
On the role of melatonin in skin physiology and pathology.
  Endocrine, 27, 137-148.  
15733542 J.A.Boutin, F.Chatelain-Egger, F.Vella, P.Delagrange, and G.Ferry (2005).
Quinone reductase 2 substrate specificity and inhibition pharmacology.
  Chem Biol Interact, 151, 213-228.  
15992934 J.A.Boutin, V.Audinot, G.Ferry, and P.Delagrange (2005).
Molecular tools to study melatonin pathways and actions.
  Trends Pharmacol Sci, 26, 412-419.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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