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PDBsum entry 1d4a

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1d4a
Jmol
Contents
Protein chain
273 a.a. *
Ligands
FAD ×4
Waters ×592
* Residue conservation analysis
PDB id:
1d4a
Name: Oxidoreductase
Title: Crystal structure of human nad[p]h-quinone oxidoreductase at 1.7 a resolution
Structure: Quinone reductase. Chain: a, b, c, d. Synonym: dt-diaphorase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.70Å     R-factor:   0.209     R-free:   0.253
Authors: M.Faig,M.A.Bianchet,S.Chen,S.Winski,D.Ross,L.M.Amzel
Key ref:
M.Faig et al. (2000). Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release. Proc Natl Acad Sci U S A, 97, 3177-3182. PubMed id: 10706635 DOI: 10.1073/pnas.050585797
Date:
01-Oct-99     Release date:   15-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P15559  (NQO1_HUMAN) -  NAD(P)H dehydrogenase [quinone] 1
Seq:
Struc:
274 a.a.
273 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.6.5.2  - NAD(P)H dehydrogenase (quinone).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NAD(P)H + a quinone = NAD(P)(+) + a hydroquinone
NAD(P)H
+ quinone
= NAD(P)(+)
+ hydroquinone
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     neuronal cell body   4 terms 
  Biological process     small molecule metabolic process   18 terms 
  Biochemical function     protein binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.050585797 Proc Natl Acad Sci U S A 97:3177-3182 (2000)
PubMed id: 10706635  
 
 
Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release.
M.Faig, M.A.Bianchet, P.Talalay, S.Chen, S.Winski, D.Ross, L.M.Amzel.
 
  ABSTRACT  
 
NAD(P)H/quinone acceptor oxidoreductase (QR1, NQO1, formerly DT-diaphorase; EC ) protects animal cells from the deleterious and carcinogenic effects of quinones and other electrophiles. In this paper we report the apoenzyme structures of human (at 1.7-A resolution) and mouse (2.8 A) QR1 and the complex of the human enzyme with the substrate duroquinone (2.5 A) (2,3,5, 6-tetramethyl-p-benzoquinone). In addition to providing a description and rationale of the structural and catalytic differences among several species, these structures reveal the changes that accompany substrate or cofactor (NAD) binding and release. Tyrosine-128 and the loop spanning residues 232-236 close the binding site, partially occupying the space left vacant by the departing molecule (substrate or cofactor). These changes highlight the exquisite control of access to the catalytic site that is required by the ping-pong mechanism in which, after reducing the flavin, NAD(P)(+) leaves the catalytic site and allows substrate to bind at the vacated position. In the human QR1-duroquinone structure one ring carbon is significantly closer to the flavin N5, suggesting a direct hydride transfer to this atom.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Schematic representation of the QR1 dimer. The numbering of the secondary element is indicated. The bound FAD is shown in one of the two sites.
Figure 4.
Fig. 4. Hydrogen bonding and van der Waals interaction observed between FAD and protein in hQR1. Open radiated circles indicate hydrophobic interactions. Hydrogen bonds are represented by dashed green lines; water molecules are shown as blue filled circles.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19941840 D.Ross, and H.Zhou (2010).
Relationships between metabolic and non-metabolic susceptibility factors in benzene toxicity.
  Chem Biol Interact, 184, 222-228.  
20630857 M.R.Middleton, R.Knox, E.Cattell, U.Oppermann, R.Midgley, R.Ali, T.Auton, R.Agarwal, D.Anderson, D.Sarker, I.Judson, T.Osawa, V.J.Spanswick, S.Davies, J.A.Hartley, and D.J.Kerr (2010).
Quinone oxidoreductase-2-mediated prodrug cancer therapy.
  Sci Transl Med, 2, 40ra50.  
20024690 P.Mazur, T.Magdziarz, A.Bak, Z.Chilmonczyk, T.Kasprzycka-Guttman, I.Misiewicz-Krzemińska, K.Skupińska, and J.Polanski (2010).
Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates?
  J Mol Model, 16, 1205-1212.  
19716833 Q.Zhang, J.Pi, C.G.Woods, and M.E.Andersen (2010).
A systems biology perspective on Nrf2-mediated antioxidant response.
  Toxicol Appl Pharmacol, 244, 84-97.  
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
19220002 M.S.King, M.S.Sharpley, and J.Hirst (2009).
Reduction of hydrophilic ubiquinones by the flavin in mitochondrial NADH:ubiquinone oxidoreductase (Complex I) and production of reactive oxygen species.
  Biochemistry, 48, 2053-2062.  
19618916 S.Sollner, S.Deller, P.Macheroux, and B.A.Palfey (2009).
Mechanism of flavin reduction and oxidation in the redox-sensing quinone reductase Lot6p from Saccharomyces cerevisiae.
  Biochemistry, 48, 8636-8643.  
18936985 T.Magdziarz, P.Mazur, and J.Polanski (2009).
Receptor independent and receptor dependent CoMSA modeling with IVE-PLS: application to CBG benchmark steroids and reductase activators.
  J Mol Model, 15, 41-51.  
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
18264564 M.A.Colucci, C.J.Moody, and G.D.Couch (2008).
Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential.
  Org Biomol Chem, 6, 637-656.  
  18703762 S.H.Audi, M.P.Merker, G.S.Krenz, T.Ahuja, D.L.Roerig, and R.D.Bongard (2008).
Coenzyme Q1 redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia.
  J Appl Physiol, 105, 1114-1126.  
18579530 Y.Fu, L.Buryanovskyy, and Z.Zhang (2008).
Quinone reductase 2 is a catechol quinone reductase.
  J Biol Chem, 283, 23829-23835.  
17571194 J.J.Newsome, E.Swann, M.Hassani, K.C.Bray, A.M.Slawin, H.D.Beall, and C.J.Moody (2007).
Indolequinone antitumour agents: correlation between quinone structure and rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase.
  Org Biomol Chem, 5, 1629-1640.  
18004453 K.Tanabe, Z.Zhang, T.Ito, H.Hatta, and S.Nishimoto (2007).
Current molecular design of intelligent drugs and imaging probes targeting tumor-specific microenvironments.
  Org Biomol Chem, 5, 3745-3757.  
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.  
17009925 U.Oppermann (2007).
Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology.
  Annu Rev Pharmacol Toxicol, 47, 293-322.  
16697277 D.H.Hyun, J.O.Hernandez, M.P.Mattson, and R.de Cabo (2006).
The plasma membrane redox system in aging.
  Ageing Res Rev, 5, 209-220.  
16552139 R.Agarwal, J.B.Bonanno, S.K.Burley, and S.Swaminathan (2006).
Structure determination of an FMN reductase from Pseudomonas aeruginosa PA01 using sulfur anomalous signal.
  Acta Crystallogr D Biol Crystallogr, 62, 383-391.
PDB codes: 1rtt 1x77
15935810 D.Ross (2005).
Functions and distribution of NQO1 in human bone marrow: potential clues to benzene toxicity.
  Chem Biol Interact, 153, 137-146.  
15964517 Y.Y.Lee, A.H.Westphal, L.H.de Haan, J.M.Aarts, I.M.Rietjens, and W.J.van Berkel (2005).
Human NAD(P)H:quinone oxidoreductase inhibition by flavonoids in living cells.
  Free Radic Biol Med, 39, 257-265.  
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
11377202 C.Breithaupt, J.Strassner, U.Breitinger, R.Huber, P.Macheroux, A.Schaller, and T.Clausen (2001).
X-ray structure of 12-oxophytodienoate reductase 1 provides structural insight into substrate binding and specificity within the family of OYE.
  Structure, 9, 419-429.
PDB codes: 1icp 1icq 1ics
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.  
11035256 S.Chen, K.Wu, and R.Knox (2000).
Structure-function studies of DT-diaphorase (NQO1) and NRH: quinone oxidoreductase (NQO2).
  Free Radic Biol Med, 29, 276-284.  
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 code is shown on the right.