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Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase.
Arch Biochem Biophys. 1997 Nov 15; 347(2):221-8.AB

Abstract

Human NAD(P)H:quinone acceptor oxidoreductase-2 (NQO2) has been prepared using an Escherichia coli expression method. NQO2 is thought to be an isoform of DT-diaphorase (EC 1.6.99.2) [also referred to as NAD(P)H:quinone acceptor oxidoreductase] because there is a 49% identity between their amino acid sequences. The present investigation has revealed that like DT-diaphorase, NQO2 is a dimer enzyme with one FAD prosthetic group per subunit. Interestingly, NQO2 uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor. It catalyzes a two-electron reduction of quinones and oxidation-reduction dyes. One-electron acceptors, such as potassium ferricyanide, cannot be reduced by NQO2. This enzyme also catalyzes a four-electron reduction, using methyl red as the electron acceptor. The NRH-methyl red reductase activity of NQO2 is 11 times the NADH-methyl red reductase activity of DT-diaphorase. In addition, through a four-electron reduction reaction, NQO2 can catalyze nitroreduction of cytotoxic compound CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. NQO2 is 3000 times more effective than DT-diaphorase in the reduction of CB 1954. Therefore, NQO2 is a NRH-dependent oxidoreductase which catalyzes two- and four-electron reduction reactions. NQO2 is resistant to typical inhibitors of DT-diaphorase, such as dicumarol, Cibacron blue, and phenindone. Flavones are inhibitors of NQO2. However, structural requirements of flavones for the inhibition of NQO2 are different from those for DT-diaphorase. The most potent flavone inhibitor tested so far is quercetin (3,5,7,3',4'-. 6pentahydroxyflavone). It has been found that quercetin is a competitive inhibitor with respect to NRH (Ki = 21 nM). NQO2 is 43 amino acids shorter than DT-diaphorase, and it has been suggested that the carboxyl terminus of DT-diaphorase plays a role in substrate binding (S. Chen et al., Protein Sci. 3, 51-57, 1994). In order to understand better the basis of catalytic differences between NQO2 and DT-diaphorase, a human NQO2 with 43 amino acids from the carboxyl terminus of human DT-diaphorase (i.e., hNQO2-hDT43) has been prepared. hNQO2-hDT43 still uses NRH as an electron donor. In addition, the chimeric enzyme is inhibited by quercetin but not dicumarol. These results suggest that additional region(s) in these enzymes is involved in differentiating NRH from NAD(P)H.

Authors+Show Affiliations

Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9367528

Citation

Wu, K, et al. "Catalytic Properties of NAD(P)H:quinone Oxidoreductase-2 (NQO2), a Dihydronicotinamide Riboside Dependent Oxidoreductase." Archives of Biochemistry and Biophysics, vol. 347, no. 2, 1997, pp. 221-8.
Wu K, Knox R, Sun XZ, et al. Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. Arch Biochem Biophys. 1997;347(2):221-8.
Wu, K., Knox, R., Sun, X. Z., Joseph, P., Jaiswal, A. K., Zhang, D., Deng, P. S., & Chen, S. (1997). Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. Archives of Biochemistry and Biophysics, 347(2), 221-8.
Wu K, et al. Catalytic Properties of NAD(P)H:quinone Oxidoreductase-2 (NQO2), a Dihydronicotinamide Riboside Dependent Oxidoreductase. Arch Biochem Biophys. 1997 Nov 15;347(2):221-8. PubMed PMID: 9367528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. AU - Wu,K, AU - Knox,R, AU - Sun,X Z, AU - Joseph,P, AU - Jaiswal,A K, AU - Zhang,D, AU - Deng,P S, AU - Chen,S, PY - 1997/12/31/pubmed PY - 1997/12/31/medline PY - 1997/12/31/entrez SP - 221 EP - 8 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 347 IS - 2 N2 - Human NAD(P)H:quinone acceptor oxidoreductase-2 (NQO2) has been prepared using an Escherichia coli expression method. NQO2 is thought to be an isoform of DT-diaphorase (EC 1.6.99.2) [also referred to as NAD(P)H:quinone acceptor oxidoreductase] because there is a 49% identity between their amino acid sequences. The present investigation has revealed that like DT-diaphorase, NQO2 is a dimer enzyme with one FAD prosthetic group per subunit. Interestingly, NQO2 uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor. It catalyzes a two-electron reduction of quinones and oxidation-reduction dyes. One-electron acceptors, such as potassium ferricyanide, cannot be reduced by NQO2. This enzyme also catalyzes a four-electron reduction, using methyl red as the electron acceptor. The NRH-methyl red reductase activity of NQO2 is 11 times the NADH-methyl red reductase activity of DT-diaphorase. In addition, through a four-electron reduction reaction, NQO2 can catalyze nitroreduction of cytotoxic compound CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. NQO2 is 3000 times more effective than DT-diaphorase in the reduction of CB 1954. Therefore, NQO2 is a NRH-dependent oxidoreductase which catalyzes two- and four-electron reduction reactions. NQO2 is resistant to typical inhibitors of DT-diaphorase, such as dicumarol, Cibacron blue, and phenindone. Flavones are inhibitors of NQO2. However, structural requirements of flavones for the inhibition of NQO2 are different from those for DT-diaphorase. The most potent flavone inhibitor tested so far is quercetin (3,5,7,3',4'-. 6pentahydroxyflavone). It has been found that quercetin is a competitive inhibitor with respect to NRH (Ki = 21 nM). NQO2 is 43 amino acids shorter than DT-diaphorase, and it has been suggested that the carboxyl terminus of DT-diaphorase plays a role in substrate binding (S. Chen et al., Protein Sci. 3, 51-57, 1994). In order to understand better the basis of catalytic differences between NQO2 and DT-diaphorase, a human NQO2 with 43 amino acids from the carboxyl terminus of human DT-diaphorase (i.e., hNQO2-hDT43) has been prepared. hNQO2-hDT43 still uses NRH as an electron donor. In addition, the chimeric enzyme is inhibited by quercetin but not dicumarol. These results suggest that additional region(s) in these enzymes is involved in differentiating NRH from NAD(P)H. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/9367528/Catalytic_properties_of_NAD_P_H:quinone_oxidoreductase_2__NQO2__a_dihydronicotinamide_riboside_dependent_oxidoreductase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(97)90344-1 DB - PRIME DP - Unbound Medicine ER -