Glutaredoxin
Encyclopedia
Glutaredoxins are small redox
enzymes of approximately one hundred amino-acid residues that use glutathione
as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxin
s, which are reduced by thioredoxin reductase
, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Oxidized glutathione is then regenerated by glutathione reductase
. Together these components compose the glutathione system.
Like thioredoxin
, 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 by the enzyme ribonucleotide reductase
. Moreover, GRX act in antioxidant defence by reducing dehydroascorbate, peroxiredoxins, and methione sulfoxide reductase. Beside their function in antioxidant defence, bacterial and plant GRX were shown to bind iron-sulfur clusters and to deliver the cluster to enzymes on demand.
. According to their redox-active centre, they are subgrouped in three classes of the CSY[C/S]-, CGSF-, and CC-type. The CC-type GRXs are only found in higher plants. In Arabidopsis GRXs are involved in flower development and Salicylic acid
signalling.
; GLRX2
; GLRX3
; GLRX5
; PTGES2
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
enzymes of approximately one hundred amino-acid residues that use glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione. In contrast to thioredoxin
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. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...
s, which are reduced by thioredoxin reductase
Thioredoxin reductase
Thioredoxin Reductases are the only known enzymes to reduce thioredoxin . Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. Both classes are flavoproteins which function as homodimers...
, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione. Oxidized glutathione is then regenerated by glutathione reductase
Glutathione reductase
Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....
. Together these components compose the glutathione system.
Like thioredoxin
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. In humans, it is encoded by the TXN gene. Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the...
, 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 by the enzyme ribonucleotide reductase
Ribonucleotide reductase
Ribonucleotide reductase is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms...
. Moreover, GRX act in antioxidant defence by reducing dehydroascorbate, peroxiredoxins, and methione sulfoxide reductase. Beside their function in antioxidant defence, bacterial and plant GRX were shown to bind iron-sulfur clusters and to deliver the cluster to enzymes on demand.
GRXs in viruses
Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed 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.GRXs in plants
Approximately 30 GRX isoforms are described in the model plant Arabidopsis thalianaArabidopsis thaliana
Arabidopsis thaliana is a small flowering plant native to Europe, Asia, and northwestern Africa. A spring annual with a relatively short life cycle, arabidopsis is popular as a model organism in plant biology and genetics...
. According to their redox-active centre, they are subgrouped in three classes of the CSY[C/S]-, CGSF-, and CC-type. The CC-type GRXs are only found in higher plants. In Arabidopsis GRXs are involved in flower development and Salicylic acid
Salicylic acid
Salicylic acid is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin...
signalling.
Human proteins containing this domain
GLRXGLRX
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 and ATP7A.-Further reading:...
; GLRX2
GLRX2
Glutaredoxin-2, mitochondrial is a protein that in humans is encoded by the GLRX2 gene.-Further reading:...
; GLRX3
GLRX3
Glutaredoxin-3 is a protein that in humans is encoded by the GLRX3 gene.-Further reading:...
; GLRX5
GLRX5
Glutaredoxin 5 also known as GLRX5 is a protein which in humans is encoded by the GLRX5 gene.- Clinical significance :Mutations in the GLRX5 gene have been associated with sideroblastic anemia....
; PTGES2
PTGES2
Prostaglandin E synthase 2 is an enzyme that in humans is encoded by the PTGES2 gene.The protein encoded by this gene is a membrane-associated prostaglandin E synthase, which catalyzes the conversion of prostaglandin H2 to prostaglandin E2...