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PDBsum entry 1qr2
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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1qr2

 

 

 

 

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Contents
Protein chain
230 a.a. *
Ligands
FAD ×2
Metals
_ZN ×2
Waters ×582
* Residue conservation analysis
PDB id:
1qr2
Name: Oxidoreductase
Title: Human quinone reductase type 2
Structure: Protein (quinone reductase type 2). Chain: a, b. Synonym: menadione reductase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: synthetic gene
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.219     R-free:   0.284
Authors: C.Foster,M.A.Bianchet,P.Talalay,L.M.Amzel
Key ref:
C.E.Foster et al. (1999). Crystal structure of human quinone reductase type 2, a metalloflavoprotein. Biochemistry, 38, 9881-9886. PubMed id: 10433694 DOI: 10.1021/bi990799v
Date:
15-Apr-99     Release date:   18-Aug-99    
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/bi990799v Biochemistry 38:9881-9886 (1999)
PubMed id: 10433694  
 
 
Crystal structure of human quinone reductase type 2, a metalloflavoprotein.
C.E.Foster, M.A.Bianchet, P.Talalay, Q.Zhao, L.M.Amzel.
 
  ABSTRACT  
 
In mammals, two separate but homologous cytosolic quinone reductases have been identified: NAD(P)H:quinone oxidoreductase type 1 (QR1) (EC 1.6.99.2) and quinone reductase type 2 (QR2). Although QR1 and QR2 are nearly 50% identical in protein sequence, they display markedly different catalytic properties and substrate specificities. We report here two crystal structures of QR2: in its native form and bound to menadione (vitamin K(3)), a physiological substrate. Phases were obtained by molecular replacement, using our previously determined rat QR1 structure as the search model. QR2 shares the overall fold of the major catalytic domain of QR1, but lacks the smaller C-terminal domain. The FAD binding sites of QR1 and QR2 are very similar, but their hydride donor binding sites are considerably different. Unexpectedly, we found that QR2 contains a specific metal binding site, which is not present in QR1. Two histidine nitrogens, one cysteine thiol, and a main chain carbonyl group are involved in metal coordination. The metal binding site is solvent-accessible, and is separated from the FAD cofactor by a distance of about 13 A.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21335006 J.Müller, and A.Hemphill (2011).
Identification of a host cell target for the thiazolide class of broad-spectrum anti-parasitic drugs.
  Exp Parasitol, 128, 145-150.  
21377769 V.Leclerc, M.Ettaoussi, M.Rami, A.Farce, J.A.Boutin, P.Delagrange, D.H.Caignard, P.Renard, P.Berthelot, and S.Yous (2011).
Design and synthesis of naphthalenic derivatives as new ligands at the melatonin binding site MT3.
  Eur J Med Chem, 46, 1622-1629.  
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
18996184 N.W.Gaikwad, L.Yang, E.G.Rogan, and E.L.Cavalieri (2009).
Evidence for NQO2-mediated reduction of the carcinogenic estrogen ortho-quinones.
  Free Radic Biol Med, 46, 253-262.  
19624732 S.Sollner, and P.Macheroux (2009).
New roles of flavoproteins in molecular cell biology: an unexpected role for quinone reductases as regulators of proteasomal degradation.
  FEBS J, 276, 4313-4324.  
19523906 T.P.Roosild, S.Castronovo, S.Miller, C.Li, T.Rasmussen, W.Bartlett, B.Gunasekera, S.Choe, and I.R.Booth (2009).
KTN (RCK) domains regulate K+ channels and transporters by controlling the dimer-hinge conformation.
  Structure, 17, 893-903.
PDB code: 3eyw
18337254 K.Ito, M.Nakanishi, W.C.Lee, Y.Zhi, H.Sasaki, S.Zenno, K.Saigo, Y.Kitade, and M.Tanokura (2008).
Expansion of substrate specificity and catalytic mechanism of azoreductase by X-ray crystallography and site-directed mutagenesis.
  J Biol Chem, 283, 13889-13896.
PDB codes: 2z98 2z9b 2z9c 2z9d
18579530 Y.Fu, L.Buryanovskyy, and Z.Zhang (2008).
Quinone reductase 2 is a catechol quinone reductase.
  J Biol Chem, 283, 23829-23835.  
  17768344 M.M.AbuKhader, J.Heap, C.I.De Matteis, S.W.Doughty, N.Minton, and M.Paoli (2007).
Crystallization and preliminary X-ray characterization of the Bacillus amyloliquefaciens YwrO enzyme.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 746-750.  
17298444 S.Sollner, R.Nebauer, H.Ehammer, A.Prem, S.Deller, B.A.Palfey, G.Daum, and P.Macheroux (2007).
Lot6p from Saccharomyces cerevisiae is a FMN-dependent reductase with a potential role in quinone detoxification.
  FEBS J, 274, 1328-1339.  
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.  
16684776 K.Ito, M.Nakanishi, W.C.Lee, H.Sasaki, S.Zenno, K.Saigo, Y.Kitade, and M.Tanokura (2006).
Three-dimensional structure of AzoR from Escherichia coli. An oxidereductase conserved in microorganisms.
  J Biol Chem, 281, 20567-20576.
PDB codes: 1v4b 2d5i
16545679 W.Wang, and A.K.Jaiswal (2006).
Nuclear factor Nrf2 and antioxidant response element regulate NRH:quinone oxidoreductase 2 (NQO2) gene expression and antioxidant induction.
  Free Radic Biol Med, 40, 1119-1130.  
16011363 A.E.Speers, and B.F.Cravatt (2005).
A tandem orthogonal proteolysis strategy for high-content chemical proteomics.
  J Am Chem Soc, 127, 10018-10019.  
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.  
16322580 J.Gorman, and L.Shapiro (2005).
Crystal structures of the tryptophan repressor binding protein WrbA and complexes with flavin mononucleotide.
  Protein Sci, 14, 3004-3012.
PDB codes: 1ydg 1yrh 1zwk 1zwl
15935811 K.Iskander, and A.K.Jaiswal (2005).
Quinone oxidoreductases in protection against myelogenous hyperplasia and benzene toxicity.
  Chem Biol Interact, 153, 147-157.  
15941714 P.Talalay (2005).
A fascination with enzymes: the journey not the arrival matters.
  J Biol Chem, 280, 28829-28847.  
12351651 D.J.Long, K.Iskander, A.Gaikwad, M.Arin, D.R.Roop, R.Knox, R.Barrios, and A.K.Jaiswal (2002).
Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity.
  J Biol Chem, 277, 46131-46139.  
11340659 G.Cavelier, and L.M.Amzel (2001).
Mechanism of NAD(P)H:quinone reductase: Ab initio studies of reduced flavin.
  Proteins, 43, 420-432.  
11514662 O.Dym, and D.Eisenberg (2001).
Sequence-structure analysis of FAD-containing proteins.
  Protein Sci, 10, 1712-1728.  
11035251 A.T.Dinkova-Kostova, and P.Talalay (2000).
Persuasive evidence that quinone reductase type 1 (DT diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen.
  Free Radic Biol Med, 29, 231-240.  
11035252 C.E.Foster, M.A.Bianchet, P.Talalay, M.Faig, and L.M.Amzel (2000).
Structures of mammalian cytosolic quinone reductases.
  Free Radic Biol Med, 29, 241-245.  
11053405 S.Miller, L.S.Ness, C.M.Wood, B.C.Fox, and I.R.Booth (2000).
Identification of an ancillary protein, YabF, required for activity of the KefC glutathione-gated potassium efflux system in Escherichia coli.
  J Bacteriol, 182, 6536-6540.  
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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