Pathways & interactions
FAD/NAD(P)-binding domain (IPR023753)
Short name: FAD/NAD-binding_dom
Overlapping homologous superfamilies
- FAD/NAD(P)-binding domain superfamily (IPR036188)
- FAD/NAD(P)-binding domain (IPR023753)
- FAD dependent oxidoreductase (IPR006076)
FAD flavoproteins belonging to the family of pyridine nucleotide-disulphide oxidoreductases (glutathione reductase, trypanothione reductase, lipoamide dehydrogenase, mercuric reductase, thioredoxin reductase, alkyl hydroperoxide reductase) share sequence similarity with a number of other flavoprotein oxidoreductases, in particular with ferredoxin-NAD+ reductases involved in oxidative metabolism of a variety of hydrocarbons (rubredoxin reductase, putidaredoxin reductase, terpredoxin reductase, ferredoxin-NAD+ reductase components of benzene 1,2-dioxygenase, toluene 1,2-dioxygenase, chlorobenzene dioxygenase, biphenyl dioxygenase), NADH oxidase and NADH peroxidase [PMID: 2319593, PMID: 1404382, PMID: 2067578]. Comparison of the crystal structures of human glutathione reductase and Escherichia coli thioredoxin reductase reveals different locations of their active sites, suggesting that the enzymes diverged from an ancestral FAD/NAD(P)H reductase and acquired their disulphide reductase activities independently [PMID: 2067578].
Despite functional similarities, oxidoreductases of this family show no sequence similarity with adrenodoxin reductases [PMID: 2924777] and flavoprotein pyridine nucleotide cytochrome reductases (FPNCR) [PMID: 1748631]. Assuming that disulphide reductase activity emerged later, during divergent evolution, the family can be referred to as FAD-dependent pyridine nucleotide reductases, FADPNR.
To date, 3D structures of glutathione reductase [PMID: 3656429], thioredoxin reductase [PMID: 2067578], mercuric reductase [PMID: 2067577], lipoamide dehydrogenase [PMID: 1880807], trypanothione reductase [PMID: 1924336] and NADH peroxidase [PMID: 1942054] have been solved. The enzymes share similar tertiary structures based on a doubly-wound alpha/beta fold, but the relative orientations of their FAD- and NAD(P)H-binding domains may vary significantly. By contrast with the FPNCR family, the folds of the FAD- and NAD(P)H-binding domains are similar, suggesting that the domains evolved by gene duplication [PMID: 7411611].
This entry describes the FAD binding domain which has a nested NADH binding domain and is found in both class I and class II oxidoreductases.
- PF07992 (Pyr_redox_2)