InterPro domain: IPR015701

Ferredoxin reductase is a member of the flavoprotein pyridine nucleotide cytochrome reductases [ 1 ] (FPNCRs) that catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. Ferredoxin reductase catalyzes the final step of electron transfer to make NADPH and ATP in plant chloroplasts during photosynthesis. Other family members include plant and fungal:

• NAD(P)H:nitrate reductases [ 2 , 2 ]
• NADH:cytochrome b5 reductases [ 3 ]
• NADPH:P450 reductases [ 4 ]
• NADPH:sulphite reductases [ 5 ]
• nitric oxide synthases [ 6 ]
• phthalate dioxygenase reductase [ 7 ]
• various other flavoproteins

Despite functional similarities, FPNCRs show no sequence similarity to NADPH:adrenodoxin reductases [ 8 ], nor to bacterial ferredoxin:NAD reductases and their homologues [ 9 ]. To date, structures for a number of family members have been solved:

• Spinacia oleracea (Spinach) ferredoxin:NADP reductase [ 10 ]
• Burkholderia cepacia (Pseudomonas cepacia) phthalate dioxygenase reductase [ 11 ]
• Zea mays (Maize) nitrate reductase flavoprotein domain [ 11 ]
• Sus scrofa (Pig) NADH:cytochrome b5 reductase [ 12 ].

In all of them, the FAD-binding domain (N-terminal) has the topology of an anti-parallel beta-barrel, while the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine dinucleotide-binding fold (i.e. a central parallel beta-sheet with 2 helices on each side) [ 13 ].

Proteins in this family also include benzoyl-CoA oxygenase component A (BoxA), which forms a complex with BoxB that catalyses the aerobic reduction/oxygenation of the aromatic ring of benzoyl-CoA to form 2,3-dihydro-2,3-dihydroxybenzoyl-CoA. BoxA also acts as a reductase that uses NADPH to reduce the oxygenase component BoxB. BoxAB does not act on NADH or benzoate [ 13 ].

1. The sequence of squash NADH:nitrate reductase and its relationship to the sequences of other flavoprotein oxidoreductases. A family of flavoprotein pyridine nucleotide cytochrome reductases. J. Biol. Chem. 266, 23542-7
2. Functional domains of assimilatory nitrate reductases and nitrite reductases. Trends Biochem. Sci. 15, 315-9
3. Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes. J. Biochem. 99, 407-22
4. An unusual yet strongly conserved flavoprotein reductase in bacteria and mammals. Trends Biochem. Sci. 16, 154-8
5. Characterization of the flavoprotein moieties of NADPH-sulfite reductase from Salmonella typhimurium and Escherichia coli. Physicochemical and catalytic properties, amino acid sequence deduced from DNA sequence of cysJ, and comparison with NADPH-cytochrome P-450 reductase. J. Biol. Chem. 264, 15796-808
6. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351, 714-8
7. Structural prototypes for an extended family of flavoprotein reductases: comparison of phthalate dioxygenase reductase with ferredoxin reductase and ferredoxin. Protein Sci. 2, 2112-33
8. cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases. Eur. J. Biochem. 180, 479-84
9. Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints. J. Mol. Biol. 212, 135-42
10. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Science 251, 60-6
11. Crystal structure of the FAD-containing fragment of corn nitrate reductase at 2.5 A resolution: relationship to other flavoprotein reductases. Structure 2, 809-21
12. Specific arrangement of three amino acid residues for flavin-binding barrel structures in NADH-cytochrome b5 reductase and the other flavin-dependent reductases. FEBS Lett. 361, 97-100
13. New enzymes involved in aerobic benzoate metabolism in Azoarcus evansii. Mol. Microbiol. 54, 223-38