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33  structures 3035  species 1  interaction 4817  sequences 11  architectures

Family: GSHPx (PF00255)

Summary: Glutathione peroxidase

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Glutathione peroxidase Edit Wikipedia article

Glutathione peroxidase
GlutPeroxidase-1GP1.png
Crystallographic structure of bovine glutathione peroxidase 1.[1]
Identifiers
EC number 1.11.1.9
CAS number 9013-66-5
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Glutathione peroxidase
Identifiers
Symbol GSHPx
Pfam PF00255
InterPro IPR000889
PROSITE PDOC00396
SCOP 1gp1
SUPERFAMILY 1gp1

Glutathione peroxidase (GPx) (EC 1.11.1.9) is the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water.

Isozymes[edit]

Several isozymes are encoded by different genes, which vary in cellular location and substrate specificity. Glutathione peroxidase 1 (GPx1) is the most abundant version, found in the cytoplasm of nearly all mammalian tissues, whose preferred substrate is hydrogen peroxide. Glutathione peroxidase 4 (GPx4) has a high preference for lipid hydroperoxides; it is expressed in nearly every mammalian cell, though at much lower levels. Glutathione peroxidase 2 is an intestinal and extracellular enzyme, while glutathione peroxidase 3 is extracellular, especially abundant in plasma.[2] So far, eight different isoforms of glutathione peroxidase (GPx1-8) have been identified in humans.

Gene Locus Enzyme
GPX1 Chr. 3 p21.3 glutathione peroxidase 1
GPX2 Chr. 14 q24.1 glutathione peroxidase 2 (gastrointestinal)
GPX3 Chr. 5 q23 glutathione peroxidase 3 (plasma)
GPX4 Chr. 19 p13.3 glutathione peroxidase 4 (phospholipid hydroperoxidase)
GPX5 Chr. 6 p21.32 glutathione peroxidase 5 (epididymal androgen-related protein)
GPX6 Chr. 6 p21 glutathione peroxidase 6 (olfactory)
GPX7 Chr. 1 p32 glutathione peroxidase 7
GPX8 Chr. 5 q11.2 glutathione peroxidase 8 (putative)

Reaction[edit]

The main reaction that glutathione peroxidase catalyzes is:

2GSH + H2O2 → GS–SG + 2H2O

where GSH represents reduced monomeric glutathione, and GS–SG represents glutathione disulfide. The mechanism involves oxidation of the selenol of a selenocysteine residue by hydrogen peroxide. This process gives the derivative with a seleninic acid (RSeOH) group. The selenenic acid is then converted back to the selenol by a two step process that begins with reaction with GSH to form the GS-SeR and water. A second GSH molecule reduces the GS-SeR intermediate back to the selenol, releasing GS-SG as the by-product. A simplified representation is shown below:[3]

RSeH + H2O2 → RSeOH + H2O
RSeOH + GSH → GS-SeR + H2O
GS-SeR + GSH → GS-SG + RSeH

Glutathione reductase then reduces the oxidized glutathione to complete the cycle:

GS–SG + NADPH + H+ → 2 GSH + NADP+.

Structure[edit]

Mammalian GPx1, GPx2, GPx3, and GPx4 have been shown to be selenium-containing enzymes, whereas GPx6 is a selenoprotein in humans with cysteine-containing homologues in rodents. GPx1, GPx2, and GPx3 are homotetrameric proteins, whereas GPx4 has a monomeric structure. As the integrity of the cellular and subcellular membranes depends heavily on glutathione peroxidase, its antioxidative protective system itself depends heavily on the presence of selenium.

Species distribution[edit]

Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are grossly phenotypically normal and have normal lifespans, indicating this enzyme is not critical for life. However, Gpx1 -/- mice develop cataracts at an early age and exhibit defects in muscle satellite cell proliferation.[2]

However, glutathione peroxidase 4 knockout mice die during early embryonic development.[2]

Some evidence, though, indicates reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.[4]

No information is available on knockouts of the other isozymes.

The bovine erythrocyte enzyme has a molecular weight of 84 kDa.

Discovery[edit]

Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.[5]

Human proteins containing this domain[edit]

GPX1; GPX2; GPX3; GPX4; GPX5;

References[edit]

  1. ^ PDB 1GP1; Epp O, Ladenstein R, Wendel A (June 1983). "The refined structure of the selenoenzyme glutathione peroxidase at 0.2-nm resolution". Eur. J. Biochem. 133 (1): 51–69. doi:10.1111/j.1432-1033.1983.tb07429.x. PMID 6852035. 
  2. ^ a b c Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558. 
  3. ^ Krishna P. Bhabak, Govindasamy Mugesh "Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants" Acc. Chem. Res., 2010, 43 (11), pp 1408–1419. doi:10.1021/ar100059g
  4. ^ Ran Q, Liang H, Ikeno Y (2007). "Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis". J. Gerontol. A Biol. Sci. Med. Sci. 62 (9): 932–42. PMID 17895430. 
  5. ^ MILLS GC (November 1957). "Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown". J. Biol. Chem. 229 (1): 189–97. PMID 13491573. 

See also[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000889

Glutathione peroxidase (GSHPx) (EC) is an enzyme that catalyses the reduction of hydroxyperoxides by glutathione [PUBMED:, PUBMED:7565867]. Its main function is to protect against the damaging effect of endogenously formed hydroxyperoxides. In higher vertebrates, several forms of GSHPx are known, including a ubiquitous cytosolic form (GSHPx-1), a gastrointestinal cytosolic form (GSHPx-GI), a plasma secreted form (GSHPx-P), and an epididymal secretory form (GSHPx-EP). In addition to these characterised forms, the sequence of a protein of unknown function [PUBMED:2771650] has been shown to be evolutionary related to those of GSHPx's.

In filarial nematode parasites, the major soluble cuticular protein (gp29) is a secreted GSHPx, which may provide a mechanism of resistance to the immune reaction of the mammalian host by neutralising the products of the oxidative burst of leukocytes [PUBMED:1631065]. The Escherichia coli protein btuE, a periplasmic protein involved in vitamin B12 transport, is evolutionarily related to GSHPxs, although the significance of this relationship is unclear. The structure of bovine seleno-glutathione peroxidase has been determined [PUBMED:6852035]. The protein belongs to the alpha-beta class, with a 3 layer(aba) sandwich architecture. The catalyic site of GSHPx contains a conserved residue which is either a cysteine or, in many eukaryotic GSHPx, a selenocysteine [PUBMED:2142875].

Gene Ontology

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Domain organisation

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Alignments

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(2461)
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  Seed
(12)
Full
(4817)
Representative proteomes NCBI
(4342)
Meta
(2461)
RP15
(446)
RP35
(800)
RP55
(1119)
RP75
(1412)
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  Seed
(12)
Full
(4817)
Representative proteomes NCBI
(4342)
Meta
(2461)
RP15
(446)
RP35
(800)
RP55
(1119)
RP75
(1412)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 12
Number in full: 4817
Average length of the domain: 104.50 aa
Average identity of full alignment: 45 %
Average coverage of the sequence by the domain: 59.73 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 108
Family (HMM) version: 14
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Species distribution

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Interactions

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GSHPx

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GSHPx domain has been found. There are 33 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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