This entry describes both class I and class II oxidoreductases.<p> 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 idref="PUB00003255"/>, <cite idref="PUB00003296"/>, <cite idref="PUB00004100"/>]. Comparison of the crystal structures of human glutathione reductase and <taxon tax_id="562">Escherichia coli</taxon> 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 [<cite idref="PUB00004100"/>]. </p><p>Despite functional similarities, oxidoreductases of this family show no sequence similarity with adrenodoxin reductases [<cite idref="PUB00001372"/>] and flavoprotein pyridine nucleotidecytochrome reductases (FPNCR) [<cite idref="PUB00002674"/>]. Assuming that disulphide reductase activity emerged later, during divergent evolution, the family can be referred to as FAD-dependent pyridine nucleotide reductases, FADPNR.</p><p>To date, 3D structures of glutathione reductase [<cite idref="PUB00003219"/>], thioredoxin reductase [<cite idref="PUB00004100"/>], mercuric reductase [<cite idref="PUB00004099"/>], lipoamide dehydrogenase [<cite idref="PUB00003272"/>], trypanothione reductase [<cite idref="PUB00004756"/>] and NADH peroxidase [<cite idref="PUB00003273"/>] 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 [<cite idref="PUB00003195"/>].</p>