Crystal structure of human quinone reductase type 2, a metalloflavoprotein.

摘要: In mammals, two separate but homologous cytosolic quinone reductases have been identified:  NAD(P)H:quinone oxidoreductase type 1 (QR1) (EC 1.6.99.2) and reductase 2 (QR2). Although QR1 QR2 are nearly 50% identical in protein sequence, they display markedly different catalytic properties substrate specificities. We report here crystal structures of QR2:  its native form bound to menadione (vitamin K3), a physiological substrate. Phases were obtained by molecular replacement, using our previously determined rat structure as the search model. shares overall fold major domain QR1, lacks smaller C-terminal domain. The FAD binding sites very similar, their hydride donor considerably different. Unexpectedly, we found that contains specific metal site, which is not present QR1. Two histidine nitrogens, one cysteine thiol, main chain carbonyl group involved coordinat...