NADPH-cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins.
The FMN-binding domain of NADPH-cytochrome P-450 oxidoreductase, residues 77-228, is homologous with bacterial flavodoxins, while the FAD-binding domain, residues 267-678, shows a high degree of similarity to two FAD-containing proteins, ferredoxin-NADP+ reductase and NADH-cytochrome b5 reductase. Comparison of these proteins to glutathione reductase, a flavoprotein whose three-dimensional structure is known, has permitted tentative identification of FAD- and cofactor-binding residues in these proteins. The remarkable conservation of sequence between NADPH-cytochrome P-450 oxidoreductase and ferredoxin-NADP+ reductase, coupled with the homology of the FMN-binding domain of the oxidoreductase with the bacterial flavodoxins, implies that NADPH-cytochrome P-450 oxidoreductase arose as a result of fusion of the ancestral genes for these two functionally linked flavoproteins.
D000595:Amino Acid Sequence; D001419:Bacteria / Q000235:genetics; D001665:Binding Sites; D005075:Biological Evolution; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005486:Flavin Mononucleotide / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism*; D005418:Flavodoxin / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics*; D011485:Protein Binding; D011487:Protein Conformation; D013045:Species Specificity
D005418:Flavodoxin; D005420:Flavoproteins; D005182:Flavin-Adenine Dinucleotide; D005486:Flavin Mononucleotide; D005287:Ferredoxin-NADP Reductase; D009251:NADPH-Ferrihemoprotein Reductase