Glutaredoxins (also known as Thioltransferase) are small

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...

enzymes of approximately one hundred amino-acid residues that use

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

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. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to

thioredoxin Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by ''TXN'' and ''TXN2'' genes. Loss-of-func ...

s, which are reduced by

thioredoxin reductase Thioredoxin reductases (TR, TrxR) () are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction ...

, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Reduced glutathione is then regenerated by

glutathione reductase Glutathione reductase (GR) also known as glutathione-disulfide reductase (GSR) is an enzyme that in humans is encoded by the GSR gene. Glutathione reductase (EC 1.8.1.7) catalyzes the reduction of glutathione disulfide (GSSG) to the sulfhydryl fo ...

. Together these components compose the glutathione system. Like

, which functions in a similar way, glutaredoxin possesses an active centre disulfide bond. 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 A deoxyribonucleotide is a nucleotide that contains deoxyribose. They are the monomeric units of the informational biopolymer, deoxyribonucleic acid ( DNA). Each deoxyribonucleotide comprises three parts: a deoxyribose sugar ( monosaccharide), a n ...

by the enzyme

ribonucleotide reductase Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of th ...

. Moreover, GRX act in antioxidant defense by reducing

dehydroascorbate Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and othe ...

peroxiredoxins Peroxiredoxins (Prxs, ; HGNC root symbol ''PRDX'') are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells. The family members in humans are PRDX ...

, and methionine sulfoxide reductase. Beside their function in antioxidant defense, bacterial and plant GRX were shown to bind

iron-sulfur clusters Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur clu ...

and to deliver the cluster to enzymes on demand.

In viruses

Glutaredoxin has been sequenced in a variety of

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

. On the basis of extensive sequence similarity, it has been proposed that ''

Vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...

'' protein O2L is, it seems, a glutaredoxin. ''

Bacteriophage T4 Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily '' Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...

'' 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 ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...

'' and 48 in Oryza sativa L. According to their redox-active centre, they are subgrouped in six classes of the CSY /S, CGFS-, CC-type and 3 groups with additional domain of unknown function. The CC-type GRXs are only found in

higher plants Vascular plants (), also called tracheophytes () or collectively Tracheophyta (), form a large group of land plants ( accepted known species) that have lignified tissues (the xylem) for conducting water and minerals throughout the plant. They al ...

. In Arabidopsis GRXs are involved in flower development and

Salicylic acid Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substance ...

signalling.

Subfamilies

*Glutaredoxin subgroup

Human proteins containing this domain

GLRX Glutaredoxin-1 is a protein that in humans is encoded by the ''GLRX'' gene. Interactions GLRX has been shown to interact with Wilson disease protein Wilson disease protein (WND), also known as ATP7B protein, is a copper-transporting P-type AT ...

;

GLRX2 Glutaredoxin 2 (GLRX2) is an enzyme that in humans encoded by the ''GLRX2'' gene. GLRX2, also known as GRX2, is a glutaredoxin family protein and a thiol-disulfide oxidoreductase that maintains cellular thiol homeostasis. This gene consists of four ...

;

GLRX3 Glutaredoxin-3 is a protein that in humans is encoded by the ''GLRX3'' gene. Interactions GLRX3 has been shown to interact with PRKCQ Protein kinase C theta (PKC-θ) is an enzyme that in humans is encoded by the ''PRKCQ'' gene. PKC-θ, a member ...

;

GLRX5 Glutaredoxin 5, also known as GLRX5, is a protein which in humans is encoded by the ''GLRX5'' gene located on chromosome 14. This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron- ...

;

PTGES2 Microsomal prostaglandin E synthase-2 (mPGES-2) or Prostaglandin E synthase 2 is an enzyme that in humans encoded by the ''PTGES2'' gene located on chromosome 9. The protein encoded by this gene is a membrane-associated prostaglandin E synthase, ...

References

External links

Enzyme database entry
* EC 1.20.4 Protein domains Single-pass transmembrane proteins Antioxidants {{1.20-enzyme-stub