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PMID: 11259642 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 7 ·2001-03-27 ·Pages 3673-8

Sun QA, Kirnarsky L, Sherman S, Gladyshev VN

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.

MeSH Terms
Amino Acid Sequence Animals Cloning, Molecular Glutathione/metabolism Glutathione Reductase Male Mice Models, Molecular Molecular Sequence Data NADH, NADPH Oxidoreductases/chemistry,genetics,metabolism Protein Conformation Sequence Homology, Amino Acid Substrate Specificity Testis/enzymology,metabolism Thioredoxin-Disulfide Reductase Thioredoxins/metabolism
Chemicals
Thioredoxins NADH, NADPH Oxidoreductases Glutathione Reductase Thioredoxin-Disulfide Reductase Txnrd3 protein, mouse Glutathione
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sun Q A
Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
Kirnarsky L
Sherman S
Gladyshev V N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.051454398
Published
2001-03-27
Epub
2001-00-20
Pages
3673-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC31110
Subset
IM
Grants
NCI NIH HHS · P30 CA036727 · United States
NIGMS NIH HHS · R01 GM061603 · United States
NIGMS NIH HHS · GM60603 · United States
NCI NIH HHS · P30 CA36727 · United States
Databases
GENBANK
AF349659
External Links
PubMed source DOI: 10.1073/pnas.051454398 PMC Full Text View journal details
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