| General information | | DisProt: | DP00727 | | Name: | Ribosyldihydronicotinamide dehydrogenase [quinone] | | Synonym(s): | NQO2_HUMAN
NRH dehydrogenase [quinone] 2
NRH:quinone oxidoreductase 2
Quinone reductase 2
QR2
NQO2
| | First appeared in release: | Release 6.00 (07/01/2012) | | UniProt: | P16083 | | UniGene: | | | SwissProt: | NQO2_HUMAN | | TrEMBL: | | | NCBI (GI): | | | Source organism: | Homo sapiens (Human) | | Sequence length: | 231 | | Percent disordered: | 7% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MAGKKVLIVY AHQEPKSFNG SLKNVAVDEL SRQGCTVTVS DLYAMNLEPR ATDKDITGTL - 60
SNPEVFNYGV ETHEAYKQRS LASDITDEQK KVREADLVIF QFPLYWFSVP AILKGWMDRV - 120
LCQGFAFDIP GFYDSGLLQG KLALLSVTTG GTAEMYTKTG VNGDSRYFLW PLQHGTLHFC - 180
GFKVLAPQIS FAPEIASEEE RKGMVAAWSQ RLQTIWKEEP IPCTAHWHFG Q
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| Functional narrative |
Function: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
CATALYTIC ACTIVITY: 1-(beta-D-ribofuranosyl)-1,4- dihydronicotinamide + a quinone = 1-(beta-D- ribofuranosyl)nicotinamide + a hydroquinone.
COFACTOR: Binds 1 zinc ion per subunit.
COFACTOR: FAD.
ENZYME REGULATION: Inhibited by melatonin, resveratrol and 5- hydroxytryptamine. Kinetic parameters: KM=28 uM for NRH; KM=11.6 uM for menadione; KM=252 uM for NADH;
SUBUNIT: Homodimer.
Subcellular Location: Cytoplasm.
MISCELLANEOUS: Uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor.
SIMILARITY: Belongs to the NAD(P)H dehydrogenase (quinone) family.
WEB RESOURCE: Name=NIEHS-SNPs; URL='http://egp.gs.washington.edu/data/nqo2/';
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | N-terminal | | Location: | 1 - 4 | | Length: | 4 | | Region sequence: |
MAGK | | Modification type: | Complex
| | PDB: | 2BZS:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- X-ray crystallography (pH: 7; NQO2 protein 10 uL; Ammonium sulfate 1.66 M; Na-HEPES 100 mM; FAD 12 uM; DTT 1 mM; CB1954 prodrug 2 mM)
| References:
- AbuKhader M, Heap J, De Matteis C, Kellam B, Doughty SW, Minton N, Paoli M. "Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex." J. Med. Chem.. 2005; 48(24): 7714-9. PubMed: 16302811
| Comments:
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| Region 2 | | Type: | Disordered | | Name: | disordered loop | | Location: | 52 - 60 | | Length: | 9 | | Region sequence: |
TDKDITGTL | | Modification type: | Complex
| | PDB: | 2B :A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- X-ray crystallography (pH: 7; Ammonium sulfate 1.66 M; CB1954 prodrug 2 mM; DTT 1 mM; FAD 12 uM; Na-HEPES 100 mM; NQO2 protein 10 uL)
| References:
- AbuKhader M, Heap J, De Matteis C, Kellam B, Doughty SW, Minton N, Paoli M. "Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex." J. Med. Chem.. 2005; 48(24): 7714-9. PubMed: 16302811
| Comments:
|
| Region 3 | | Type: | Disordered | | Name: | C-terminal | | Location: | 228 - 231 | | Length: | 4 | | Region sequence: |
HFGQ | | Modification type: | Complex
| | PDB: | 2BZS:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- X-ray crystallography (pH: 7; Ammonium sulfate 1.66 M; CB1954 prodrug 2 mM; DTT 1 mM; FAD 12 uM; Na-HEPES 100 mM; NQO2 protein 10 uL)
| References:
- AbuKhader M, Heap J, De Matteis C, Kellam B, Doughty SW, Minton N, Paoli M. "Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex." J. Med. Chem.. 2005; 48(24): 7714-9. PubMed: 16302811
| Comments:
|
| References |
- Calamini B, Santarsiero BD, Boutin JA, Mesecar AD. "Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2." Biochem. J.. 2008; 413(1): 81-91. PubMed: 18254726
- Fu Y, Buryanovskyy L, Zhang Z. "Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954." Biochem. Biophys. Res. Commun.. 2005; 336(1): 332-8. PubMed: 16129418
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| Comments |
Additional PDB structures for NQO2 protein:
. Crystal structure from Fu et al (2005), PDB 1XI2, is NQO2 in complex with cancer prodrug CB1954.
. Crystal structure from Calamini et al (2008), PDB 2QX6, is NQO2 in complex with melatonin and melatonin anologue.
. Crystal structure from Jansson et al (2005), PDB 1ZX1, is NQO2 in complex with cytostatic prodrug CB1954.
AV sent 6-26-2012 (PMID:16302811)
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