Structures of mammalian cytosolic quinone reductases

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 quino nes by a two-electron reduction mechanism, thus averting production of radi cals. QR1 is expressed in the cytoplasm of many tissues, and is highly indu cible. A closely related homologue, quinone reductase type 2 (QR2), hi-is b een identified in several mammalian species. QR2 is also capable of reducin g quinones to hydroquinones, but unlike QR1, cannot use NAD(P)H. X-ray crys tallographic 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. (C) 2000 Elsevier Science Inc.