Peroxiredoxin

Peroxiredoxins (Prxs, EC 1.11.1.15) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells.

Classification
Peroxiredoxins can be regulated by changes to phosphorylation, redox and possibly oligomerization states. They are divided into three classes: typical 2-Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate. The recycling of the sulfenic acid back to a thiol is what distinguishes the three enzyme classes, 2-Cys peroxiredoxins are reduced by thiols such as glutathione, while the 1-Cys enzymes may be reduced by ascorbic acid or glutathione in the presence of GST-π. Using crystal structures, a detailed catalytic cycle has been derived for typical 2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed to control enzyme activity. Inactivation of these enzymes by over-oxidation of the active thiol to sulfinic acid can be reversed by sulfiredoxin.

Peroxiredoxins are frequently referred to as alkyl hydroperoxide reductase (AhpC) in bacteria. Other names include thiol specific antioxidant (TSA). This family contains AhpC and TSA, as well as related proteins.

Mammals express six peroxiredoxins:
 * 1-Cys enzymes: PRDX6
 * 2-Cys enzymes: PRDX1, PRDX2, PRDX3, PRDX4, and PRDX5

Function
The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2) as well as studies in knockout mice. Mice lacking peroxiredoxin 1 or 2 develop severe haemolytic anemia, and are predisposed to certain haematopoietic cancers. Peroxiredoxin 1 knockout mice have a 15% reduction in lifespan. Peroxiredoxin 6 knockout mice are viable and do not display obvious gross pathology, but are more sensitive to certain exogenous sources of oxidative stress, such as hyperoxia. Peroxiredoxin 3 (mitochondrial matrix peroxiredoxin) knockout mice are viable and do not display obvious gross pathology.

Plant 2-Cys peroxiredoxins are post-translationally targeted to chloroplasts, where they protect the photosynthetic membrane against photooxidative damage. Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA.

Circadian clock
Peroxiredoxins are the oldest common mechanism responsible for the 24-hour internal circadian clock of almost all life on earth.