NADPH-cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins

Biochemistry. 1986 Apr 8;25(7):1682-7. doi: 10.1021/bi00355a036.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacteria / genetics
  • Binding Sites
  • Biological Evolution*
  • Ferredoxin-NADP Reductase / genetics
  • Flavin Mononucleotide / metabolism*
  • Flavin-Adenine Dinucleotide / metabolism*
  • Flavodoxin / genetics
  • Flavoproteins / genetics
  • NADPH-Ferrihemoprotein Reductase / genetics*
  • Protein Binding
  • Protein Conformation
  • Species Specificity


  • Flavodoxin
  • Flavoproteins
  • Flavin-Adenine Dinucleotide
  • Flavin Mononucleotide
  • Ferredoxin-NADP Reductase
  • NADPH-Ferrihemoprotein Reductase