Glutathione peroxidase
Glutathione peroxidase (GSHPx) is an enzyme that catalyses the reduction of hydroxyperoxides by glutathione. Its main function is to protect against the damaging effect of endogenously formed hydroxyperoxides.
Reference Protein and Structure
- Sequence
-
P00435
(1.11.1.9)
(Sequence Homologues)
(PDB Homologues)
- Biological species
-
Bos taurus (Cattle)
- PDB
-
1gp1
- THE REFINED STRUCTURE OF THE SELENOENZYME GLUTATHIONE PEROXIDASE AT 0.2-NM RESOLUTION
(2.0 Å)
- Catalytic CATH Domains
-
3.40.30.10
(see all for 1gp1)
- Cofactors
- Water (1)
Enzyme Reaction (EC:1.11.1.9)
+
→
+
Alternative enzyme names: GSH peroxidase, Reduced glutathione peroxidase, Selenium-glutathione peroxidase,
Enzyme Mechanism
Introduction
Reaction is initiated by the nucleophilic attack of selenocysteine on the hydroperoxide. On collision with a hydroperoxide, the active-site selenium is readily oxidised to a selenenic acid derivative, which thereafter must be reduced to terminate the catalytic cycle.
Catalytic Residues Roles
| UniProt | PDB* (1gp1) | ||
| Sec52 | SE745A | The redox active component of the catalytic triad. Acts as a nucleophile attacking the hydrogen peroxide and is later regenerated by glutathione. | covalent catalysis, proton shuttle (general acid/base) |
| Trp165 | Trp158A | Part of the catalytic triad. Computational studies have suggested that this residue acts as a general acid/base. It is hydrogen-bonding distance from the selenium of the peroxidatic Sec and helps activate the selenol, which facilitates the nucleophilic attack on the hydroperoxide | proton shuttle (general acid/base) |
| Gln87 | Gln80A | Forms a catalytic triad. It is hydrogen-bonding distance from the selenium of the peroxidatic Sec and helps activate the selenol, which facilitates the nucleophilic attack on the hydroperoxide | electrostatic stabiliser |
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file;
y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain;
C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.
Chemical Components
References
- Orian L et al. (2015), Free Radic Biol Med, 87, 1-14. Selenocysteine oxidation in glutathione peroxidase catalysis: an MS-supported quantum mechanics study. DOI:10.1016/j.freeradbiomed.2015.06.011. PMID:26163004.
- Pannala VR et al. (2014), Free Radic Res, 48, 487-502. A mechanistic mathematical model for the catalytic action of glutathione peroxidase. DOI:10.3109/10715762.2014.886775. PMID:24456207.
- Tosatto SC et al. (2008), Antioxid Redox Signal, 10, 1515-1526. The catalytic site of glutathione peroxidases. DOI:10.1089/ars.2008.2055. PMID:18500926.
- Barnett YA et al. (1995), Mutat Res, 338, 115-128. An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. PMID:7565867.
- Maiorino M et al. (1995), Biol Chem Hoppe Seyler, 376, 651-660. Probing the presumed catalytic triad of selenium-containing peroxidases by mutational analysis of phospholipid hydroperoxide glutathione peroxidase (PHGPx). PMID:8962674.
- Epp O et al. (1983), Eur J Biochem, 133, 51-69. The refined structure of the selenoenzyme glutathione peroxidase at 0.2-nm resolution. DOI:10.2210/pdb1gp1/pdb. PMID:6852035.
Catalytic Residues Roles
| Residue | Roles |
|---|---|
| SE745A | covalent catalysis, proton shuttle (general acid/base) |
| Trp158A | proton shuttle (general acid/base) |
| Gln80A | electrostatic stabiliser |