NADPH-cytochrome P450 oxidoreductase: Prototypic member of the diflavin reductase family

► This review covers structure and mechanism of NADPH-cytochrome P450 oxidoreductase and the reductase domains of nitric oxide synthases. ► The enzymes catalyze electron transfer from NADPH to FAD to FMN to the heme center of cytochrome P450 or of the NOS oxygenase domains. ► The enzymes contain distinct FAD and FMN domains that are connected by a flexible hinge. ► Two flavin domains undergo large domain movements during catalysis.