EzCatDB: S00522
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DB codeS00522
CATH domainDomain 13.40.50.360 : Rossmann foldCatalytic domain
E.C.1.10.99.2

CATH domainRelated DB codes (homologues)
3.40.50.360 : Rossmann foldS00343,M00006,M00154

Enzyme Name
UniProtKBKEGG

P16083
Protein nameRibosyldihydronicotinamide dehydrogenase {quinone}ribosyldihydronicotinamide dehydrogenase (quinone)
NRH:quinone oxidoreductase 2
NQO2
NQO2
NAD(P)H:quinone oxidoreductase-2 (misleading)
QR2
quinone reductase 2
N-ribosyldihydronicotinamide dehydrogenase (quinone)
NAD(P)H:quinone oxidoreductase2 (misleading)
SynonymsEC 1.10.99.2
NRH dehydrogenase {quinone} 2
NRH:quinone oxidoreductase 2
Quinone reductase 2
QR2
RefSeqNP_000895.2 (Protein)
NM_000904.3 (DNA/RNA sequence)
PfamPF02525 (Flavodoxin_2)
[Graphical view]


UniProtKB:Accession NumberP16083
Entry nameNQO2_HUMAN
Activity1-(beta-D-ribofuranosyl)-1,4- dihydronicotinamide + a quinone = 1-(beta-D- ribofuranosyl)nicotinamide + a hydroquinone.
SubunitHomodimer.
Subcellular locationCytoplasm.
CofactorBinds 1 zinc ion per subunit.,FAD.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00016C00038C00005C00004C00080C01628C00006C00003C05850
CompoundFADZincNADPHNADHH+Vitamin KNADP+NAD+Reduced Vitamin K
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideheavy metalamide group,amine group,nucleotideamide group,amine group,nucleotideothersaromatic ring (only carbon atom),carbohydrate,lipidamide group,amine group,nucleotideamide group,amine group,nucleotidearomatic ring (only carbon atom),carbohydrate,lipid
ChEBI16238
29105
16474
16908
15378

18009
15846

PubChem643975
32051
5884
439153
1038

5886
5893

                 
1qr2ABound:FADBound:_ZNUnboundUnbound UnboundUnboundUnboundUnbound
1qr2BBound:FADBound:_ZNUnboundUnbound UnboundUnboundUnboundUnbound
2qr2ABound:FADBound:_ZNUnboundUnbound Bound:VK3UnboundUnboundUnbound
2qr2BBound:FADBound:_ZNUnboundUnbound Bound:VK3UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P16083 & literature [7]
pdbCatalytic residuesCofactor-binding residues
          
1qr2AGLY 149;TYR 155
HIS 173;HIS 177;CYS 222(Zinc binding)
1qr2BGLY 149;TYR 155
HIS 173;HIS 177;CYS 222(Zinc binding)
2qr2AGLY 149;TYR 155
HIS 173;HIS 177;CYS 222(Zinc binding)
2qr2BGLY 149;TYR 155
HIS 173;HIS 177;CYS 222(Zinc binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]Fig.8, p.8849-8850
[6]p.612-614
[7]p.9985-9986
[10]p.278-279
[13]Fig.1, Fig.4, p.130-131
[14]p.244
[15]p.664-665
[19]Fig.8

references
[1]
PubMed ID1510975
JournalBiochemistry
Year1992
Volume31
Pages7879-85
AuthorsSiegel D, Beall H, Senekowitsch C, Kasai M, Arai H, Gibson NW, Ross D
TitleBioreductive activation of mitomycin C by DT-diaphorase.
[2]
PubMed ID7530954
JournalBiochem Pharmacol
Year1995
Volume49
Pages127-40
AuthorsCadenas E
TitleAntioxidant and prooxidant functions of DT-diaphorase in quinone metabolism.
[3]
CommentsX-ray crystallography
PubMed ID7568029
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages8846-50
AuthorsLi R, Bianchet MA, Talalay P, Amzel LM
TitleThe three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction.
Related PDB1qrd
[4]
PubMed ID8999809
JournalJ Biol Chem
Year1997
Volume272
Pages1437-9
AuthorsChen S, Knox R, Wu K, Deng PS, Zhou D, Bianchet MA, Amzel LM
TitleMolecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse.
[5]
PubMed ID9050836
JournalProc Natl Acad Sci U S A
Year1997
Volume94
Pages1669-74
AuthorsZhao Q, Yang XL, Holtzclaw WD, Talalay P
TitleUnexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase).
[6]
PubMed ID10917652
JournalBiochem Soc Trans
Year1999
Volume27
Pages610-5
AuthorsBianchet MA, Foster C, Faig M, Talalay P, Amzel LM
TitleStructure and mechanism of cytosolic quinone reductases.
[7]
CommentsX-ray crystallography
PubMed ID10433694
JournalBiochemistry
Year1999
Volume38
Pages9881-6
AuthorsFoster CE, Bianchet MA, Talalay P, Zhao Q, Amzel LM
TitleCrystal structure of human quinone reductase type 2, a metalloflavoprotein.
Related PDB1qr2,2qr2
[8]
CommentsX-ray crystallography
PubMed ID10543876
JournalJ Med Chem
Year1999
Volume42
Pages4325-30
AuthorsSkelly JV, Sanderson MR, Suter DA, Baumann U, Read MA, Gregory DS, Bennett M, Hobbs SM, Neidle S
TitleCrystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954).
Related PDB1qbg
[9]
PubMed ID10419545
JournalMol Pharmacol
Year1999
Volume56
Pages272-8
AuthorsChen S, Wu K, Zhang D, Sherman M, Knox R, Yang CS
TitleMolecular characterization of binding of substrates and inhibitors to DT-diaphorase: combined approach involving site-directed mutagenesis, inhibitor-binding analysis, and computer modeling.
[10]
PubMed ID11035256
JournalFree Radic Biol Med
Year2000
Volume29
Pages276-84
AuthorsChen S, Wu K, Knox R
TitleStructure-function studies of DT-diaphorase (NQO1) and NRH: quinone oxidoreductase (NQO2).
[11]
PubMed ID10877993
JournalFront Biosci
Year2000
Volume5
PagesD639-48
AuthorsBeall HD, Winski SI
TitleMechanisms of action of quinone-containing alkylating agents. I: NQO1-directed drug development.
[12]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID20202608
PubMed ID10706635
JournalProc Natl Acad Sci U S A
Year2000
Volume97
Pages3177-82
AuthorsFaig M, Bianchet MA, Talalay P, Chen S, Winski S, Ross D, Amzel LM
TitleStructures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release.
Related PDB1d4a,1dxo,1dxq
Related UniProtKBP15559
[13]
PubMed ID10694883
JournalTrends Biochem Sci
Year2000
Volume25
Pages126-32
AuthorsFraaije MW, Mattevi A
TitleFlavoenzymes: diverse catalysts with recurrent features.
[14]
PubMed ID11035252
JournalFree Radic Biol Med
Year2000
Volume29
Pages241-5
AuthorsFoster CE, Bianchet MA, Talalay P, Faig M, Amzel LM
TitleStructures of mammalian cytosolic quinone reductases.
[15]
CommentsX-ray crystallography
PubMed ID11587640
JournalStructure (Camb)
Year2001
Volume9
Pages659-67
AuthorsFaig M, Bianchet MA, Winski S, Hargreaves R, Moody CJ, Hudnott AR, Ross D, Amzel LM
TitleStructure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones.
Related PDB1gg5,1h66,1h69
[16]
CommentsX-ray crystallography
PubMed ID11735396
JournalBiochemistry
Year2001
Volume40
Pages15135-42
AuthorsWinski SL, Faig M, Bianchet MA, Siegel D, Swann E, Fung K, Duncan MW, Moody CJ, Amzel LM, Ross D
TitleCharacterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches.
Related PDB1kbo,1kbq
[17]
PubMed ID11340659
JournalProteins
Year2001
Volume43
Pages420-32
AuthorsCavelier G, Amzel LM
TitleMechanism of NAD(P)H:quinone reductase: Ab initio studies of reduced flavin.
[18]
PubMed ID12147263
JournalArch Biochem Biophys
Year2002
Volume404
Pages254-62
AuthorsAnusevicius Z, Sarlauskas J, Cenas N
TitleTwo-electron reduction of quinones by rat liver NAD(P)H:quinone oxidoreductase: quantitative structure-activity relationships.
[19]
PubMed ID15078100
JournalBiochemistry
Year2004
Volume43
Pages4538-47
AuthorsKwiek JJ, Haystead TA, Rudolph J
TitleKinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines.

comments
This enzyme has a similar catalytic mechanism to that of QR1 (S00343 in EzCatDB), alghough it is slightly different. This enzyme involves a metal ion in catalysis (see [7]).

createdupdated
2004-10-262009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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