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Glutathione peroxidase

  Contact author: Marcia Pinheiro Margis

  Last update: 2016-12-09 (Catherine Mathe)

Glutathione peroxidase from Animals (Metazoa), Insect (Metazoa), Plants (Viridiplantae), Fungi-Bacteria and other (bacteria, fungus and protist)

Glutathione peroxidase:
Pfam: PF00255, GSHPx; 1.
Interpro: IPR000889, Glut_peroxidase; IPR012336, Thiordxn-like_fd and IPR012335, Thioredoxin_fold

Description Glutathione peroxidase are included in haem-free thiol peroxidase family as well as Peroxiredoxins (Prx). Both families, although totally different from their primary sequence, have in common the formation of a sulfenic acid on a catalytic cysteine during the first step of peroxide reduction.

Glutathione peroxidase (EC for classical glutathione peroxidase and EC phospholipid-hydroperoxide glutathione peroxidase) encompases a family of multiple isozymes, which catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols using reduced glutathione.

2 glutathione + H2O2 glutathione disulfide + 2 H2O.

2 glutathione + lipid hydroperoxide glutathione disulfide + lipid + 2 H2O

Some of these isozymes have selenium-dependent glutathione peroxidase activity, with selenocysteine been encoded by an opal TGA codon, while others do not contain any selenocysteine (Brown et al., 2000).
The animal glutathione peroxidase family is characterized by the presence of a conserved motif (GPx signature 1) containing a totally conserved cysteine or selenocysteine residue (G[K/R]x[L/V][I/L]I[V/E/T]NVA[S/T/A][E/Q/L/Y][C/U]G[L/T]T). It is almost totally dependent on GSH for its regeneration. Other non animal �so called� glutathione peroxidases characterized so far possess at least two conserved cysteines which form a disulfide bridge reduced by thioredoxin but not GSH. Similar motif containing one of the cystein is still present in plants: VNVAS[R/K/Q]CG, bacteria: VN[T/V]A[S/T/A][R/K/E/Q/A]CG and fungi: VN[T/V]AS[K/R/H/L]C[G/S/A]. The initial definition based on homology to animal glutathione peroxidase is thus not adapted anymore as these enzymes are thioredoxin-dependent peroxidases.
Two other conserved domains can be found in GPx: a glutathione peroxidase signature 2 (LAFPCNQF), and WNF(S/T)KF that are critical sites for the catalytic activity of this enzyme (Churin et al., 1999). Photosynthetic organisms contain three conserved cystein instead of two: the third Cys is outside the classical GPX catalytic domain (Iqbal et al., 2006). A third Cys, in similar position, can also be found in members from fungi.
In mammalian tissues there are four major selenium dependent GPx isozymes: i) classical GPx (GPx-1) which is found in red cells, liver, lung and kidney; ii) gastrointestinal GPx (GPx-2), iii) plasma GPx (GPx-3), which is present in different organs such as kidney, lung, epididymus, vas deferens, placenta, seminal vesicle, heart, and muscle, and iv) phospholipid GPx (PHGPx-4), which also present a broad distribution in different tissues. The divers GPx also have distinct subcellular locations: GPx1 was identified in cytosol, nucleus and mitochondria; GPx2 in cytosol and nucleus; GPx3 is a secreted protein also found in cytosol, GPx4 is present in nucleus, cytosol, mitochondria and bound to membranes (Herbette et al., 2007). Two other GPx isozymes, GPx-5 and 6, have been identified in mammalian tissues. (Thisse et al. 2003) and are close related to GPx3. GPx7 compose the seventh and less characterizes group of mammalian GPxs.

In plant glutathione peroxidase protein or transcript increased in response to: salt stress (Holland et al., 1993), mechanical stimulation (Dep�ge et al., 1998), hydrogen peroxide treatment (Levine et al., 1994), and pathogen infections (Levine et al., 1994).
Literature Brown KM, Pickard K, Nicol F, Beckett GJ, Duthie GG, Arthur JR. Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphoctyes, granulocytes, platelets and erythrocytes. Clin Sci (Lond). 2000 May;98(5):593-9. PMID: 10781391

Churin Y, Schilling S, Borner T. A gene family encoding glutathione peroxidase homologues in Hordeum vulgare (barley). A gene family encoding glutathione peroxidase homologues in Hordeum vulgare (barley). FEBS Lett. 1999 Oct 1;459(1):33-8. PMID: 10508912

Depege N, Drevet J, Boyer N. Molecular cloning and characterization of tomato cDNA encoding glutathione peroxidaselike proteins. Eur J Biochem. 1998 Apr 15;253(2):445-51. PMID: 9654095

Herbette S, Roeckel-Drevet P, Drevet JR. Seleno-independent glutathione peroxidases. FEBS J. 2007 May;274(9):2163-80. Review. PMID: 17419737

Holland D, Ben-Hayyim G, Faltin Z, Camoin L, Strosberg AD, Eshdat Y. Molecular characterization of salt-stressassociated protein in citrus: protein and cDNAsequence similarity tomammalian glutathione peroxidase. Plant Mol Biol. 1993 Mar;21(5):923-7. PMID: 8467085

Iqbal A, Yabuta Y, Takeda T, Nakano Y, Shigeoka S (2006) Hydroperoxide reduction by thioredoxin-specific glutathione peroxidase isoenzymes of Arabidopsis thaliana. FEBS J. 2006 Dec;273(24):5589-97. PMID: 17096689

Levine A, Tenhaken R, Dixon R, Lamb C. H2O2 from oxidative burst orchestrates the plant hypersensitive disease resistance response. Cell. 1994 Nov 18;79(4):583-93. PMID: 7954825

Thisse C, Degrave A, Kryukov GV, Gladyshev VN, Obrecht-Pflumio S, Krol A, Thisse B, Lescure A. Spatial and temporal expression patterns of selenoprotein genes during embryogenesis in zebrafish. Gene Expr Patterns. 2003 Aug;3(4):525-32. PMID: 12915322
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