催化性能的NAD (P) H:醌oxidoreductase-2 (NQO2),一个dihydronicotinamide核糖甙依赖型氧化还原酶。
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吴K,诺克斯R,太阳XZ贾斯瓦尔AK,约瑟夫·P D,邓PS,陈
催化性能的NAD (P) H:醌oxidoreductase-2 (NQO2),一个dihydronicotinamide核糖甙依赖型氧化还原酶。
拱生物化学Biophys。1997年11月15日,347 (2):221 - 8。
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9367528 (在PubMed]
- 文摘
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人类NAD (P) H:醌受体oxidoreductase-2 (NQO2)已经准备使用一个大肠杆菌表达方法。NQO2 DT-diaphorase的被认为是对碘氧基苯甲醚(EC 1.6.99.2)(也称为NAD (P) H:醌受体氧化还原酶)因为有49%的身份之间的氨基酸序列。目前的调查揭示,像DT-diaphorase NQO2是一时尚辅基的二聚体酶亚基。有趣的是,NQO2使用dihydronicotinamide核糖甙(NRH)而不是NAD (P) H作为电子供体。它催化双电子减少醌类和氧化还原染料。单电子受体,如铁氰化钾,不能减少NQO2。这种酶催化four-electron减少,使用甲基红作为电子受体。NQO2 NRH-methyl红色还原酶活动的11倍NADH-methyl红DT-diaphorase还原酶活性。此外,通过four-electron还原反应,NQO2可以催化nitroreduction 1954细胞毒性化合物CB [5 - (aziridin-1-yl) 2, 4-dinitrobenzamide]。NQO2 3000倍比1954年减少CB DT-diaphorase更有效。 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.