EC 1.11.1.27 - Glutathione-dependent peroxiredoxin

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IntEnz Enzyme Nomenclature
EC 1.11.1.27

Names

Accepted name:
glutathione-dependent peroxiredoxin
Systematic name:
glutathione:hydroperoxide oxidoreductase

Reaction

Comments:

Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins. The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Glutathione-dependent peroxiredoxins have been reported from bacteria and animals, and appear to be 1-Cys enzymes. The mechanism for the mammalian PRDX6 enzyme involves heterodimerization of the enzyme with π-glutathione S-transferase, followed by glutathionylation of the oxidized cysteine residue. Subsequent dissociation of the heterodimer yields glutathionylated peroxiredoxin, which is restored to the active form via spontaneous reduction by a second glutathione molecule. Formerly EC 1.11.1.15.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot: (14) [show] [UniProt]

References

  1. Wood, Z. A., Schroder, E., Robin Harris, J., Poole, L. B.
    Structure, mechanism and regulation of peroxiredoxins.
    Trends Biochem. Sci. 28 : 32-40 (2003). [PMID: 12517450]
  2. Pauwels, F., Vergauwen, B., Vanrobaeys, F., Devreese, B., Van Beeumen, J. J.
    Purification and characterization of a chimeric enzyme from Haemophilus influenzae Rd that exhibits glutathione-dependent peroxidase activity.
    J. Biol. Chem. 278 : 16658-16666 (2003). [PMID: 12606554]
  3. Manevich, Y., Feinstein, S. I., Fisher, A. B.
    Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with pi GST.
    Proc. Natl. Acad. Sci. U.S.A. 101 : 3780-3785 (2004). [PMID: 15004285]
  4. Greetham, D., Grant, C. M.
    Antioxidant activity of the yeast mitochondrial one-Cys peroxiredoxin is dependent on thioredoxin reductase and glutathione in vivo.
    Mol. Cell. Biol. 29 : 3229-3240 (2009). [PMID: 19332553]
  5. Lim, J. G., Bang, Y. J., Choi, S. H.
    Characterization of the Vibrio vulnificus 1-Cys peroxiredoxin Prx3 and regulation of its expression by the Fe-S cluster regulator IscR in response to oxidative stress and iron starvation.
    J. Biol. Chem. 289 : 36263-36274 (2014). [PMID: 25398878]

[EC 1.11.1.27 created 1983 as EC 1.11.1.15, part transferred 2020 to EC 1.11.1.27]