D
IPR014025

Glutaredoxin subgroup

InterPro entry
Short nameGlutaredoxin_subgr
Overlapping
homologous
superfamilies
 
domain relationships

Description

Glutaredoxins
[7, 2, 10]
, also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system
[6]
.

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond
[1]
. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates
[5, 4, 9, 8]
. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed
[3]
that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This entry represents a conserved region including the active site of this enzyme.

References

1.The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues. Foloppe N, Nilsson L. Structure 12, 289-300, (2004). View articlePMID: 14962389

2.Thioredoxin and glutaredoxin: small multi-functional redox proteins with active-site disulphide bonds. Holmgren A. Biochem. Soc. Trans. 16, 95-6, (1988). PMID: 3286320

3.Vaccinia virus encodes a protein with similarity to glutaredoxins. Johnson GP, Goebel SJ, Perkus ME, Davis SW, Winslow JP, Paoletti E. Virology 181, 378-81, (1991). View articlePMID: 1994586

4.Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction. Berardi MJ, Bushweller JH. J. Mol. Biol. 292, 151-61, (1999). View articlePMID: 10493864

5.Reactivity of the human thioltransferase (glutaredoxin) C7S, C25S, C78S, C82S mutant and NMR solution structure of its glutathionyl mixed disulfide intermediate reflect catalytic specificity. Yang Y, Jao S, Nanduri S, Starke DW, Mieyal JJ, Qin J. Biochemistry 37, 17145-56, (1998). View articlePMID: 9860827

6.Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Fernandes AP, Holmgren A. Antioxid. Redox Signal. 6, 63-74, (2004). View articlePMID: 14713336

7.Thioredoxin and related proteins in procaryotes. Gleason FK, Holmgren A. FEMS Microbiol. Rev. 4, 271-97, (1988). PMID: 3152490

8.Glutaredoxin: role in reversible protein s-glutathionylation and regulation of redox signal transduction and protein translocation. Shelton MD, Chock PB, Mieyal JJ. Antioxid. Redox Signal. 7, 348-66, (2005). View articlePMID: 15706083

9.Catalysis of thiol/disulfide exchange. Glutaredoxin 1 and protein-disulfide isomerase use different mechanisms to enhance oxidase and reductase activities. Xiao R, Lundstrom-Ljung J, Holmgren A, Gilbert HF. J. Biol. Chem. 280, 21099-106, (2005). View articlePMID: 15814611

10.Thioredoxin and glutaredoxin systems. Holmgren A. J. Biol. Chem. 264, 13963-6, (1989). View articlePMID: 2668278

Cross References

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