Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems

Qi An Sun, Leo Kirnarsky, Simon Sherman, Vadim N. Gladyshev

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3673-3678
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number7
DOIs
StatePublished - Mar 27 2001

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Selenoproteins
Thioredoxins
Glutathione Disulfide
Glutathione
Oxidoreductases
Glutaredoxins
Disulfides
Thioredoxin-Disulfide Reductase
Oxidation-Reduction
Deoxyribonucleotides
Electrons
Selenocysteine
Terminator Codon
Substrate Specificity
Signal Transduction
Nucleotides
Antioxidants
Apoptosis
Enzymes
Growth

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. / Sun, Qi An; Kirnarsky, Leo; Sherman, Simon; Gladyshev, Vadim N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 7, 27.03.2001, p. 3673-3678.

Research output: Contribution to journalArticle

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