Glutaredoxin Explained

Glutaredoxins^{[1] [2] [3]} (also known as Thioltransferase) are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. In humans this oxidation repair enzyme is also known to participate in many cellular functions, including redox signaling and regulation of glucose metabolism.^{[4] [5]} Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Reduced glutathione is then regenerated by glutathione reductase. Together these components compose the glutathione system.^[6]

Like thioredoxin, which functions in a similar way, glutaredoxin possesses an active centre disulfide bond.^[7] It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Glutaredoxins function as electron carriers in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase.^[6] Moreover, GRX act in antioxidant defense by reducing dehydroascorbate, peroxiredoxins, and methionine sulfoxide reductase. Beside their function in antioxidant defense, bacterial and plant GRX were shown to bind iron-sulfur clusters and to deliver the cluster to enzymes on demand.^[8]

In viruses

Glutaredoxin has been sequenced in a variety of viruses. On the basis of extensive sequence similarity, it has been proposed^[9] that Vaccinia virus protein O2L is, it seems, a glutaredoxin. Bacteriophage T4 thioredoxin seems to be evolution-related. In position 5 of the pattern T4, thioredoxin has Val instead of Pro.

In plants

Approximately 30 GRX isoforms are described in the model plant Arabidopsis thaliana and 48 in Oryza sativa L. According to their redox-active centre, they are subgrouped in six classes of the CSY[C/S]-, CGFS-, CC-type and 3 groups with additional domain of unknown function. The CC-type GRXs are only found in higher plants. In Arabidopsis GRXs are involved in flower development and Salicylic acid signalling.

Subfamilies

• Glutaredoxin subgroup

Human proteins containing this domain

GLRX

GLRX2; GLRX3; GLRX5; PTGES2

External links

• Enzyme database entry

Notes and References

1. Gleason FK, Holmgren A . Thioredoxin and related proteins in procaryotes . FEMS Microbiology Reviews . 54 . 4 . 271–97 . December 1988 . 3152490 . 10.1111/j.1574-6968.1988.tb02747.x . free .
2. Holmgren A . Thioredoxin and glutaredoxin: small multi-functional redox proteins with active-site disulphide bonds . Biochemical Society Transactions . 16 . 2 . 95–6 . April 1988 . 3286320 . 10.1042/bst0160095 .
3. Holmgren A . Thioredoxin and glutaredoxin systems . The Journal of Biological Chemistry . 264 . 24 . 13963–6 . August 1989 . 10.1016/S0021-9258(18)71625-6 . 2668278 . free .
4. Xing KY, Lou MF . Effect of age on the thioltransferase (glutaredoxin) and thioredoxin systems in the human lens . Investigative Ophthalmology & Visual Science . 51 . 12 . 6598–604 . December 2010 . 20610843 . 10.1167/iovs.10-5672 . 3055771 .
5. Berndt C, Lillig CH, Holmgren A . Thioredoxins and glutaredoxins as facilitators of protein folding . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1783 . 4 . 641–50 . April 2008 . 18331844 . 10.1016/j.bbamcr.2008.02.003 . Redox regulation of protein folding . free .
6. Fernandes AP, Holmgren A . Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system . Antioxidants & Redox Signaling . 6 . 1 . 63–74 . February 2004 . 14713336 . 10.1089/152308604771978354 .
7. Foloppe N, Nilsson L . The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues . Structure . 12 . 2 . 289–300 . February 2004 . 14962389 . 10.1016/j.str.2004.01.009 . free .
8. Rouhier N, Lemaire SD, Jacquot JP . The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation . Annual Review of Plant Biology . 59 . 143–66 . 2008 . 18444899 . 10.1146/annurev.arplant.59.032607.092811 .
9. Johnson GP, Goebel SJ, Perkus ME, Davis SW, Winslow JP, Paoletti E . Vaccinia virus encodes a protein with similarity to glutaredoxins . Virology . 181 . 1 . 378–81 . March 1991 . 1994586 . 10.1016/0042-6822(91)90508-9 .