Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems.
Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and further supply electrons for deoxyribonucleotide synthesis, antioxidant defense, and redox regulation of signal transduction, transcription, cell growth, and apoptosis. We cloned and characterized a pyridine nucleotide disulfide oxidoreductase, Trx and GSSG reductase (TGR), that exhibits specificity for both redox systems. This enzyme contains a selenocysteine residue encoded by the TGA codon. TGR can reduce Trx, GSSG, and a GSH-linked disulfide in in vitro assays. This unusual substrate specificity is achieved by an evolutionary conserved fusion of the TR and glutaredoxin domains. These observations, together with the biochemical probing and molecular modeling of the TGR structure, suggest a mechanism whereby the C-terminal selenotetrapeptide serves a role of a protein-linked GSSG and shuttles electrons from the disulfide center within the TR domain to either the glutaredoxin domain or Trx.
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Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
Kirnarsky
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Sherman
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Gladyshev
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D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology* / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase; D013879:Thioredoxins / Q000378:metabolism*
D013879:Thioredoxins; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C424443:Txnrd3 protein, mouse; D005978:Glutathione