Peroxiredoxin

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AhpC-TSA
Peroxiredoxin.png
Structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium.
Identifiers
Symbol AhpC-TSA
Pfam PF00578
Pfam clan CL0172
InterPro IPR000866
SCOP 1prx
SUPERFAMILY 1prx
OPM superfamily 139
OPM protein 1xvw
peroxiredoxin
Identifiers
EC number 1.11.1.15
CAS number Template:CAS
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Peroxiredoxins (Prxs, EC 1.11.1.15; HGNC root symbol PRDX) are a ubiquitous family of antioxidant enzymes that also control cytokine-induced peroxide levels and thereby mediate signal transduction in mammalian cells.[1] The family members in humans are PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, and PRDX6. The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2).

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.[2] 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.[3] 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.[4] Inactivation of these enzymes by over-oxidation of the active thiol to sulfinic acid can be reversed by sulfiredoxin.[5]

Peroxiredoxins are frequently referred to as alkyl hydroperoxide reductase (AhpC) in bacteria.[6] Other names include thiol specific antioxidant (TSA).[7] This family contains AhpC and TSA, as well as related proteins.

Mammals express six peroxiredoxins:[8]

Enzyme regulation

This protein may use the morpheein model of allosteric regulation.[9]

Function

Peroxiredoxin uses thioredoxin (Trx) to recharge after reducing hydrogen peroxide (H2O2) in the following reactions:[10]

  • Prx(reduced) + H2O2 → Prx(oxidized) + 2H2O
  • Prx(oxidized) + Trx(reduced) → Prx(reduced) + Trx(oxidized)

The oxidized form of Prx is inactive, requiring the donation of electrons from reduced Trx to restore its catalytic activity.[11]

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.[12] 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.[13] Peroxiredoxin 3 (mitochondrial matrix peroxiredoxin) knockout mice are viable and do not display obvious gross pathology. Peroxiredoxins are proposed to play a role in cell signaling by regulating H2O2 levels.[14]

Plant 2-Cys peroxiredoxins are post-translationally targeted to chloroplasts,[15] where they protect the photosynthetic membrane against photooxidative damage.[16] Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA.[17]

Circadian clock

Peroxiredoxins have been implicated in the 24-hour internal circadian clock of many organisms.[18][19][20]

See also

References

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This article incorporates text from the public domain Pfam and InterPro IPR000866

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