InterPro: IPR001709 Flavoprotein pyridine nucleotide cytochrome reductase

Flavoprotein pyridine nucleotide cytochrome reductases [1] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. The enzymes include ferredoxin:NADP⁺reductases (FNR) [2], plant and fungal NAD(P)H:nitrate reductases [1, 3], NADH:cytochrome b5 reductases [4], NADPH:P450 reductases [5], NADPH:sulphite reductases [6], nitric oxide synthases [7], phthalate dioxygenase reductase [8], and various other flavoproteins.

Despite functional similarities, FPNCRs show no sequence similarity to NADPH:adrenodoxin reductases [9], nor to bacterial ferredoxin:NAD⁺reductases and their homologues [10]. To date, 3D-structures of 4 members of the family have been solved: Spinacia oleracea (Spinach) ferredoxin:NADP⁺ reductase [11]; Burkholderia cepacia (Pseudomonas cepacia) phthalate dioxygenase reductase [8]; the flavoprotein domain of Zea mays (Maize) nitrate reductase [12]; and Sus scrofa (Pig) NADH:cytochrome b5 reductase [13]. 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) [8]. In spite of such structural similarities, the level of amino acid identity between family members is at or below the limit of significance (e.g., nitrate reductase is only 15% identical to FNR) [12].