DB code: S00522

CATH domain 3.40.50.360 : Rossmann fold Catalytic domain
E.C. 1.10.99.2
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.360 : Rossmann fold S00343 M00006 M00154

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P16083 Ribosyldihydronicotinamide dehydrogenase {quinone}
EC 1.10.99.2
NRH dehydrogenase {quinone} 2
NRH:quinone oxidoreductase 2
Quinone reductase 2
QR2
NP_000895.2 (Protein)
NM_000904.3 (DNA/RNA sequence)
PF02525 (Flavodoxin_2)
[Graphical View]

KEGG enzyme name
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)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P16083 NQO2_HUMAN 1-(beta-D-ribofuranosyl)-1,4- dihydronicotinamide + a quinone = 1-(beta-D- ribofuranosyl)nicotinamide + a hydroquinone. Homodimer. Cytoplasm. Binds 1 zinc ion per subunit. FAD.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00016 C00038 C00005 C00004 C00080 C01628 C00006 C00003 C05850
E.C.
Compound FAD Zinc NADPH NADH H+ Vitamin K NADP+ NAD+ Reduced Vitamin K
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide heavy metal amide group,amine group,nucleotide amide group,amine group,nucleotide others aromatic ring (only carbon atom),carbohydrate,lipid amide group,amine group,nucleotide amide group,amine group,nucleotide aromatic ring (only carbon atom),carbohydrate,lipid
ChEBI 16238
29105
16474
16908
15378
18009
15846
PubChem 643975
32051
5884
439153
1038
5886
5893
1qr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound
1qr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Bound:_ZN Unbound Unbound Unbound Unbound Unbound Unbound
2qr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Bound:_ZN Unbound Unbound Bound:VK3 Unbound Unbound Unbound
2qr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FAD Bound:_ZN Unbound Unbound Bound:VK3 Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P16083 & literature [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 149;TYR 155 HIS 173;HIS 177;CYS 222(Zinc binding)
1qr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 149;TYR 155 HIS 173;HIS 177;CYS 222(Zinc binding)
2qr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 149;TYR 155 HIS 173;HIS 177;CYS 222(Zinc binding)
2qr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLY 149;TYR 155 HIS 173;HIS 177;CYS 222(Zinc binding)

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 1510975
Journal Biochemistry
Year 1992
Volume 31
Pages 7879-85
Authors Siegel D, Beall H, Senekowitsch C, Kasai M, Arai H, Gibson NW, Ross D
Title Bioreductive activation of mitomycin C by DT-diaphorase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7530954
Journal Biochem Pharmacol
Year 1995
Volume 49
Pages 127-40
Authors Cadenas E
Title Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7568029
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 8846-50
Authors Li R, Bianchet MA, Talalay P, Amzel LM
Title The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction.
Related PDB 1qrd
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8999809
Journal J Biol Chem
Year 1997
Volume 272
Pages 1437-9
Authors Chen S, Knox R, Wu K, Deng PS, Zhou D, Bianchet MA, Amzel LM
Title Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9050836
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 1669-74
Authors Zhao Q, Yang XL, Holtzclaw WD, Talalay P
Title Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase).
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10917652
Journal Biochem Soc Trans
Year 1999
Volume 27
Pages 610-5
Authors Bianchet MA, Foster C, Faig M, Talalay P, Amzel LM
Title Structure and mechanism of cytosolic quinone reductases.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10433694
Journal Biochemistry
Year 1999
Volume 38
Pages 9881-6
Authors Foster CE, Bianchet MA, Talalay P, Zhao Q, Amzel LM
Title Crystal structure of human quinone reductase type 2, a metalloflavoprotein.
Related PDB 1qr2 2qr2
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10543876
Journal J Med Chem
Year 1999
Volume 42
Pages 4325-30
Authors Skelly JV, Sanderson MR, Suter DA, Baumann U, Read MA, Gregory DS, Bennett M, Hobbs SM, Neidle S
Title Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954).
Related PDB 1qbg
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10419545
Journal Mol Pharmacol
Year 1999
Volume 56
Pages 272-8
Authors Chen S, Wu K, Zhang D, Sherman M, Knox R, Yang CS
Title Molecular characterization of binding of substrates and inhibitors to DT-diaphorase: combined approach involving site-directed mutagenesis, inhibitor-binding analysis, and computer modeling.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11035256
Journal Free Radic Biol Med
Year 2000
Volume 29
Pages 276-84
Authors Chen S, Wu K, Knox R
Title Structure-function studies of DT-diaphorase (NQO1) and NRH: quinone oxidoreductase (NQO2).
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10877993
Journal Front Biosci
Year 2000
Volume 5
Pages D639-48
Authors Beall HD, Winski SI
Title Mechanisms of action of quinone-containing alkylating agents. I: NQO1-directed drug development.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 20202608
PubMed ID 10706635
Journal Proc Natl Acad Sci U S A
Year 2000
Volume 97
Pages 3177-82
Authors Faig M, Bianchet MA, Talalay P, Chen S, Winski S, Ross D, Amzel LM
Title Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release.
Related PDB 1d4a 1dxo 1dxq
Related UniProtKB P15559
[13]
Resource
Comments
Medline ID
PubMed ID 10694883
Journal Trends Biochem Sci
Year 2000
Volume 25
Pages 126-32
Authors Fraaije MW, Mattevi A
Title Flavoenzymes: diverse catalysts with recurrent features.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 11035252
Journal Free Radic Biol Med
Year 2000
Volume 29
Pages 241-5
Authors Foster CE, Bianchet MA, Talalay P, Faig M, Amzel LM
Title Structures of mammalian cytosolic quinone reductases.
Related PDB
Related UniProtKB
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11587640
Journal Structure (Camb)
Year 2001
Volume 9
Pages 659-67
Authors Faig M, Bianchet MA, Winski S, Hargreaves R, Moody CJ, Hudnott AR, Ross D, Amzel LM
Title Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones.
Related PDB 1gg5 1h66 1h69
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11735396
Journal Biochemistry
Year 2001
Volume 40
Pages 15135-42
Authors Winski SL, Faig M, Bianchet MA, Siegel D, Swann E, Fung K, Duncan MW, Moody CJ, Amzel LM, Ross D
Title Characterization of a mechanism-based inhibitor of NAD(P)H:quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches.
Related PDB 1kbo 1kbq
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11340659
Journal Proteins
Year 2001
Volume 43
Pages 420-32
Authors Cavelier G, Amzel LM
Title Mechanism of NAD(P)H:quinone reductase: Ab initio studies of reduced flavin.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 12147263
Journal Arch Biochem Biophys
Year 2002
Volume 404
Pages 254-62
Authors Anusevicius Z, Sarlauskas J, Cenas N
Title Two-electron reduction of quinones by rat liver NAD(P)H:quinone oxidoreductase: quantitative structure-activity relationships.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 15078100
Journal Biochemistry
Year 2004
Volume 43
Pages 4538-47
Authors Kwiek JJ, Haystead TA, Rudolph J
Title Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines.
Related PDB
Related UniProtKB

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]).

Created Updated
2004-10-26 2009-02-26