FAD/NAD(P)-binding domain
IPR023753
Definition
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. this domain seems to include contains the pair of redox-active cysteines involved in the transfer of reducing equivalents from the FAD cofactor to the substrate. 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 [[cite:PMID:2319593], [cite:PMID:1404382], [cite: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 α/β 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.
11 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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