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.[1] 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.[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]
Alkyl hydroperoxide reductase (AhpC) is a bacterial enzyme responsible for directly reducing organic hyperoxides in its reduced dithiol form.[6] Thiol specific antioxidant (TSA) is a physiologically important antioxidant which constitutes an enzymatic defense against sulphur-containing radicals.[7] This family contains AhpC and TSA, as well as related proteins.
Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans.[8] This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an Arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.
The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 1) as well as studies in knockout mice. Mice lacking peroxiredoxin 1 or 2 develop severe haemolytic anemia, and are predisposed to certain haematopoetic 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 hyperoxida [9]. 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 [10], where they protect the photosynthetic membrane against photooxidative damage [11]. Nuclear gene expression depends on chloroplast-to-nucleus signalling and responds to photosynthetic signals, such as the acceptor availability at photosystem II and ABA [12].
See also
References
- ^ 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:. PMID 15917183.
- ^ Claiborne A, Yeh J, Mallett T, Luba J, Crane E, Charrier V, Parsonage D (1999). "Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation". Biochemistry 38 (47): 15407–16. doi:. PMID 10569923.
- ^ Monteiro G, Horta BB, Pimenta DC, Augusto O, Netto LE (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:. PMID 17360337. http://www.pnas.org/cgi/content/full/104/12/4886.
- ^ Wood Z, Schröder E, Robin Harris J, Poole L (2003). "Structure, mechanism and regulation of peroxiredoxins". Trends Biochem Sci 28 (1): 32–40. doi:. PMID 12517450.
- ^ Jönsson TJ, Lowther WT (2007). "The peroxiredoxin repair proteins". Sub-cellular biochemistry 44: 115–41. doi:. PMID 18084892. PMC 2391273. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18084892.
- ^ Poole L (2005). "Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases". Arch Biochem Biophys 433 (1): 240–54. doi:. PMID 15581580.
- ^ Chae H, Rhee S (1994). "A thiol-specific antioxidant and sequence homology to various proteins of unknown function". Biofactors 4 (3-4): 177–80. PMID 7916964.
- ^ WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)
- ^ Muller, F. L., Lustgarten, M. S., Jang, Y., Richardson, A. and Van Remmen, H. (2007) Trends in oxidative aging theories. Free Radic. Biol. Med. 43, 477-503
- ^ Baier, M. and Dietz K-J (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. The Plant Journal 12, 179-190
- ^ Baier, M. and Dietz K-J (1999) protective function of chloroplast 2-Cysteine peroxiredoxin in photosynthesis. Evidence from transgenic Arabidopsis. Plant Physiology 119, 1407-1414
- ^ Baier, M., Stroeher, E. and Dietz K-J (1997) The acceptor availability at photosystem I and ABA control nuclear expression of 2-Cys peroxiredoxin-A in Arabidopsis thaliana. Plant Cell Physiol. 45, 997-1006
This article uses material from the open-source database Pfam link
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