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Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship
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Molecular cloning and analysis of the gene encoding the NADH oxidase
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cDNA sequence of adrenodoxin reductase. Identification of NADP-binding
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Refined structure of glutathione reductase at 1.54A resolution.
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Refined crystal structure of lipoamide dehydrogenase from Azotobacter
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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 . Comparison of the crystal structures of
human glutathione reductase and E.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 .
Despite functional similarities, oxidoreductases of this family show no
sequence similarity with adrenodoxin reductases  and flavoprotein
pyridine nucleotide cytochrome reductases (FPNCR) . 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
, thioredoxin reductase , mercuric reductase , lipoamide
dehydrogenase , trypanothione reductase  and NADH peroxidase 
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 .
FADPNR is a 5-element fingerprint that provides a signature for the
FAD-dependent pyridine nucleotide reductase family. The fingerprint
was derived from an initial alignment of 20 sequences: motifs 3 and 4
contain conserved Gly residues involved in binding the FAD flavin moiety.
Nine iterations on SPTR57.15_40.15f were required to reach convergence, at
which point a true set comprising 5,455 sequences was identified. Numerous
partial matches were also found, all of which are family members that fail
to make significant matches with one or more motifs.