Structures of mammalian cytosolic quinone reductases

• Published in: Free radical biology & medicine Vol. 29; no. 3; pp. 241 - 245
• Main Authors: Foster, Christine E, Bianchet, Mario A, Talalay, Paul, Faig, Margarita, Amzel, L.Mario
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2000
• Subjects: Animals; Binding Sites; Coenzymes - metabolism; Crystallography, X-Ray; Cytosol - enzymology; Flavoprotein; Free radicals; Humans; Hydride transfer; Metalloprotein; Metals - metabolism; Models, Molecular; NAD(P)H:quinone oxidocreductase; Protein Conformation; Quinone Reductases - chemistry; Quinone Reductases - metabolism; Quinones - metabolism; QR2; QR1; Free radicals; Metalloprotein; FMN; FAD; Hydride transfer; NAD(P)H; Flavoprotein; NAD(P)H:quinone oxidocreductase
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(00)00299-9

The metabolism of quinone compounds presents one source of oxidative stress in mammals, as many pathways proceed by mechanisms that generate reactive oxygen species as by-products. One defense against quinone toxicity is the enzyme NAD(P)H:quinone oxidoreductase type 1 (QR1), which metabolizes quinones by a two-electron reduction mechanism, thus averting production of radicals. QR1 is expressed in the cytoplasm of many tissues, and is highly inducible. A closely related homologue, quinone reductase type 2 (QR2), has been identified in several mammalian species. QR2 is also capable of reducing quinones to hydroquinones, but unlike QR1, cannot use NAD(P)H. X-ray crystallographic studies of QR1 and QR2 illustrate that despite their different biochemical properties, these enzymes have very similar three-dimensional structures. In particular, conserved features of the active sites point to the close relationship between these two enzymes.