NAD(P)H dehydrogenase, quinone 2
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
NAD(P)H dehydrogenase, quinone 2, also known as QR2, is a protein that in humans is encoded by the NQO2 gene. It is a phase II detoxification enzyme which can carry out two or four electron reductions of quinones. Its mechanism of reduction is through a ping-pong mechanism involving its FAD cofactor. Initially in a reductive phase NQO2 binds to reduced dihydronicotinamide riboside (NRH) electron donor, and mediates a hydride transfer from NRH to FAD. Then, in an oxidative phase, NQO2 binds to its quinone substrate and reduces the quinone to a dihydroquinone. Besides the two catalytic FAD, NQO2 also has two zinc ions. It is not clear whether the metal has a catalytic role. NQO2 is a paralog of NQO1.
NQO2 is a homodimer. NQO2 can be inhibited by resveratrol.{{cite web | title = Entrez Gene: NQO2 NAD(P)H dehydrogenase, quinone 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4835}} One of QR2's binding sites responds to 2-iodomelatonin, and has been referred to as MT3.{{cite journal |vauthors=Cardinali DP, Delagrange P, Dubocovich ML, Jockers R, Krause DN, Markus RP, Olcese J, Pintor J, Renault N, Sugden D, Tosini G, Zlotos DP |title=Melatonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database |journal= IUPHAR/BPS Guide to Pharmacology CITE |date=2019 |volume=2019 |issue=4 |doi=10.2218/gtopdb/F39/2019.4|doi-access=free }}
References
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Further reading
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- {{cite journal | vauthors=Jaiswal AK, Burnett P, Adesnik M, McBride OW |title=Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6. |journal=Biochemistry |volume=29 |issue= 7 |pages= 1899–906 |year= 1990 |pmid= 1691923 |doi=10.1021/bi00459a034 }}
- {{cite journal | author=Jaiswal AK |title=Human NAD(P)H:quinone oxidoreductase2. Gene structure, activity, and tissue-specific expression. |journal=J. Biol. Chem. |volume=269 |issue= 20 |pages= 14502–8 |year= 1994 |doi=10.1016/S0021-9258(17)36651-6 |pmid= 8182056 |doi-access=free }}
- {{cite journal | vauthors=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) |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 5 |pages= 1669–74 |year= 1997 |pmid= 9050836 |doi=10.1073/pnas.94.5.1669 | pmc=19974 |bibcode=1997PNAS...94.1669Z |doi-access=free }}
- {{cite journal |vauthors=Wu K, Knox R, Sun XZ, etal |title=Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. |journal=Arch. Biochem. Biophys. |volume=347 |issue= 2 |pages= 221–8 |year= 1997 |pmid= 9367528 |doi= 10.1006/abbi.1997.0344 }}
- {{cite journal |vauthors=Foster CE, Bianchet MA, Talalay P, etal |title=Crystal structure of human quinone reductase type 2, a metalloflavoprotein. |journal=Biochemistry |volume=38 |issue= 31 |pages= 9881–6 |year= 1999 |pmid= 10433694 |doi= 10.1021/bi990799v }}
- {{cite journal | vauthors=Jaiswal AK, Bell DW, Radjendirane V, Testa JR |title=Localization of human NQO1 gene to chromosome 16q22 and NQO2-6p25 and associated polymorphisms. |journal=Pharmacogenetics |volume=9 |issue= 3 |pages= 413–8 |year= 1999 |pmid= 10471077 |doi=10.1097/00008571-199906000-00020 }}
- {{cite journal | vauthors=Harada S, Fujii C, Hayashi A, Ohkoshi N |title=An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. |journal=Biochem. Biophys. Res. Commun. |volume=288 |issue= 4 |pages= 887–92 |year= 2001 |pmid= 11688992 |doi= 10.1006/bbrc.2001.5868 }}
- {{cite journal | vauthors=Strassburg A, Strassburg CP, Manns MP, Tukey RH |title=Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. |journal=Mol. Pharmacol. |volume=61 |issue= 2 |pages= 320–5 |year= 2002 |pmid= 11809856 |doi=10.1124/mol.61.2.320 }}
- {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }}
- {{cite journal | vauthors=Okubo T, Harada S, Higuchi S, Matsushita S |title=Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms. |journal=Alcohol. Clin. Exp. Res. |volume=27 |issue= 8 Suppl |pages= 68S–71S |year= 2004 |pmid= 12960511 |doi= 10.1097/01.ALC.0000078616.63296.41 }}
- {{cite journal |vauthors=Ostrousky O, Meged S, Loewenthal R, etal |title=NQO2 gene is associated with clozapine-induced agranulocytosis. |journal=Tissue Antigens |volume=62 |issue= 6 |pages= 483–91 |year= 2004 |pmid= 14617031 |doi=10.1046/j.1399-0039.2003.00133.x }}
- {{cite journal | vauthors=Harada S, Tachikawa H, Kawanishi Y |title=A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia. |journal=Psychiatr. Genet. |volume=13 |issue= 4 |pages= 205–9 |year= 2005 |pmid= 14639047 |doi= 10.1097/00041444-200312000-00003 |s2cid=37313428 }}
- {{cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |s2cid=21903526 |doi-access=free }}
- {{cite journal | vauthors=Kwiek JJ, Haystead TA, Rudolph J |title=Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. |journal=Biochemistry |volume=43 |issue= 15 |pages= 4538–47 |year= 2004 |pmid= 15078100 |doi= 10.1021/bi035923w }}
- {{cite journal |vauthors=Buryanovskyy L, Fu Y, Boyd M, etal |title=Crystal structure of quinone reductase 2 in complex with resveratrol. |journal=Biochemistry |volume=43 |issue= 36 |pages= 11417–26 |year= 2004 |pmid= 15350128 |doi= 10.1021/bi049162o |pmc=3650734 }}
- {{cite journal | vauthors=Wang W, Jaiswal AK |title=Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter. |journal=Free Radic. Biol. Med. |volume=37 |issue= 8 |pages= 1231–43 |year= 2005 |pmid= 15451063 |doi= 10.1016/j.freeradbiomed.2004.06.042 }}
- {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}
- {{cite journal | vauthors=Hsieh TC, Wang Z, Hamby CV, Wu JM |title=Inhibition of melanoma cell proliferation by resveratrol is correlated with upregulation of quinone reductase 2 and p53. |journal=Biochem. Biophys. Res. Commun. |volume=334 |issue= 1 |pages= 223–30 |year= 2005 |pmid= 15993843 |doi= 10.1016/j.bbrc.2005.06.073 }}
- {{cite journal | vauthors=Fu Y, Buryanovskyy L, Zhang Z |title=Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954. |journal=Biochem. Biophys. Res. Commun. |volume=336 |issue= 1 |pages= 332–8 |year= 2005 |pmid= 16129418 |doi= 10.1016/j.bbrc.2005.08.081 }}
- {{cite journal |vauthors=Rual JF, Venkatesan K, Hao T, etal |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 }}
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External links
- {{PDBe-KB2|P16083|Ribosyldihydronicotinamide dehydrogenase [quinone]}}
{{PDB Gallery|geneid=4835}}
{{gene-6-stub}}