Oxidoreductases;
Acting on a peroxide as acceptor;
Peroxidases
BRITE hierarchy

glutathione:hydroperoxide oxidoreductase

2 glutathione + ROOH = glutathione disulfide + H2O + ROH [RN:R12578]

R12578
Reaction

glutathione [CPD:C00051];
ROOH [CPD:C15498]

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 [1]. 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) (see {single/111115a::mechanism}). 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 pi-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.

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