From Wikipedia, the free encyclopedia
  (Redirected from Peroxiredoxins)
Jump to: navigation, search
Structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium.
Symbol AhpC-TSA
Pfam PF00578
Pfam clan CL0172
InterPro IPR000866
SCOP 1prx
OPM superfamily 139
OPM protein 1xvw
EC number
CAS number 207137-51-7
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Peroxiredoxins (Prxs, EC; 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).


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[edit]

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


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[edit]

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

See also[edit]


  1. ^ Rhee S, Chae H, Kim K (2005). "Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling". Free Radic Biol Med. 38 (12): 1543–52. doi:10.1016/j.freeradbiomed.2005.02.026. PMID 15917183. 
  2. ^ Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ, Charrier V, Parsonage D (November 1999). "Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation". Biochemistry. 38 (47): 15407–16. doi:10.1021/bi992025k. PMID 10569923. 
  3. ^ Monteiro G, Horta BB, Pimenta DC, Augusto O, Netto LE (March 2007). "Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C". Proc. Natl. Acad. Sci. U.S.A. 104 (12): 4886–91. doi:10.1073/pnas.0700481104. PMC 1829234free to read. PMID 17360337. 
  4. ^ Wood ZA, Schröder E, Robin Harris J, Poole LB (January 2003). "Structure, mechanism and regulation of peroxiredoxins". Trends Biochem. Sci. 28 (1): 32–40. doi:10.1016/S0968-0004(02)00003-8. PMID 12517450. 
  5. ^ Jönsson TJ, Lowther WT (2007). "The peroxiredoxin repair proteins". Subcell. Biochem. Subcellular Biochemistry. 44: 115–41. doi:10.1007/978-1-4020-6051-9_6. ISBN 978-1-4020-6050-2. PMC 2391273free to read. PMID 18084892. 
  6. ^ Poole LB (January 2005). "Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases". Arch. Biochem. Biophys. 433 (1): 240–54. doi:10.1016/ PMID 15581580. 
  7. ^ Chae HZ, Rhee SG (May 1994). "A thiol-specific antioxidant and sequence homology to various proteins of unknown function". BioFactors. 4 (3–4): 177–80. PMID 7916964. 
  8. ^ Kim SY, Jo HY, Kim MH, Cha YY, Choi SW, Shim JH, Kim TJ, Lee KY (November 2008). "H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of iPLA2 activity". J. Biol. Chem. 283 (48): 33563–8. doi:10.1074/jbc.M806578200. PMC 2662274free to read. PMID 18826942. 
  9. ^ Selwood T, Jaffe EK (March 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/ PMC 3298769free to read. PMID 22182754. 
  10. ^ Rhee SG, Kang SW, Chang TS, Jeong W, Kim K (July 2001). "Peroxiredoxin, a novel family of peroxidases". IUBMB Life. 52 (1–2): 35–41. doi:10.1080/15216540252774748. PMID 11795591. 
  11. ^ Pillay CS, Hofmeyr JH, Olivier BG, Snoep JL, Rohwer JM (January 2009). "Enzymes or redox couples? The kinetics of thioredoxin and glutaredoxin reactions in a systems biology context". Biochem. J. 417 (1): 269–75. doi:10.1042/BJ20080690. PMID 18694397. 
  12. ^ Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA (July 2003). "Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression". Nature. 424 (6948): 561–5. doi:10.1038/nature01819. PMID 12891360. 
  13. ^ Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558. 
  14. ^ Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS, Woo HA (April 2005). "Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins". Curr. Opin. Cell Biol. 17 (2): 183–9. doi:10.1016/ PMID 15780595. 
  15. ^ Baier M, Dietz KJ (July 1997). "The plant 2-Cys peroxiredoxin BAS1 is a nuclear-encoded chloroplast protein: its expressional regulation, phylogenetic origin, and implications for its specific physiological function in plants". Plant J. 12 (1): 179–90. doi:10.1046/j.1365-313X.1997.12010179.x. PMID 9263459. 
  16. ^ Baier M, Dietz KJ (April 1999). "Protective function of chloroplast 2-cysteine peroxiredoxin in photosynthesis. Evidence from transgenic Arabidopsis". Plant Physiol. 119 (4): 1407–14. doi:10.1104/pp.119.4.1407. PMC 32026free to read. PMID 10198100. 
  17. ^ Baier M, Ströher E, Dietz KJ (August 2004). "The acceptor availability at photosystem I and ABA control nuclear expression of 2-Cys peroxiredoxin-A in Arabidopsis thaliana". Plant Cell Physiol. 45 (8): 997–1006. doi:10.1093/pcp/pch114. PMID 15356325. 
  18. ^ Bass J, Takahashi JS (January 2011). "Circadian rhythms: Redox redux". Nature. 469 (7331): 476–8. doi:10.1038/469476a. PMC 3760156free to read. PMID 21270881. Lay summaryScience News. 
  19. ^ O'Neill JS, Reddy AB (January 2011). "Circadian clocks in human red blood cells". Nature. 469 (7331): 498–503. doi:10.1038/nature09702. PMC 3040566free to read. PMID 21270888. 
  20. ^ O'Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget FY, Reddy AB, Millar AJ (January 2011). "Circadian rhythms persist without transcription in a eukaryote". Nature. 469 (7331): 554–8. doi:10.1038/nature09654. PMC 3040569free to read. PMID 21270895. 

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