Function
Peroxiredoxin (Prx) is an antioxidant enzyme. In the Prxs the active-site Cys is oxidized to sulfenic acid hyper oxide forming a Cys-SOH intermediate. A second Cys residue resolves the intermediate to a protein disulfide bond. The Prxs are divided into 3 types according to their intermediate resolving mechanism: typical 2-Cysteine Prx in which the Cys-Cys bond is formed between two subunits, atypical 2-Cys Prx in which the bond is formed within one subunit and 1-Cysteine Prx which uses a single Cys residue for the catalysis. Prx Q is the plant homolog of Bacterioferritin comigratory protein.
Typical 2-Cys Prx
- Prx 1 interacts with signaling molecules[1].
- Prx 2 is essential for sustaining erythrocyte life span[2].
- Prx 3 is mitochondria-specific.[3].
- Prx 4 localizes to the cytoplasm and regulates the activation of NF-κB[4].
Atypical 2-Cys Prx
- Prx 5 protects from mitochondrial DNA damage induced by H2O2[5].
1-Cys Prx
- Prx 6 reduces peroxidized membrane phospholipids[6].
Relevance
Prx are over expressed in cancer tissue[7]. Prx 4 mediates osteoclast activation in cancer cells[8].
Structural highlights
In the typical 2-cysteine Prx the Cys-Cys bond is formed between two subunits[9]. Cl coordination site. Water molecules is shown as red sphere.
3D Structures of Peroxiredoxin
Peroxiredoxin 3D structures
- ↑ Neumann CA, Cao J, Manevich Y. Peroxiredoxin 1 and its role in cell signaling. Cell Cycle. 2009 Dec 15;8(24):4072-8. Epub 2009 Dec 5. PMID:19923889 doi:https://dx.doi.org/10.4161/cc.8.24.10242
- ↑ Low FM, Hampton MB, Winterbourn CC. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid Redox Signal. 2008 Sep;10(9):1621-30. doi: 10.1089/ars.2008.2081. PMID:18479207 doi:https://dx.doi.org/10.1089/ars.2008.2081
- ↑ Chang TS, Cho CS, Park S, Yu S, Kang SW, Rhee SG. Peroxiredoxin III, a mitochondrion-specific peroxidase, regulates apoptotic signaling by mitochondria. J Biol Chem. 2004 Oct 1;279(40):41975-84. Epub 2004 Jul 27. PMID:15280382 doi:https://dx.doi.org/10.1074/jbc.M407707200
- ↑ Fujii J, Ikeda Y, Kurahashi T, Homma T. Physiological and pathological views of peroxiredoxin 4. Free Radic Biol Med. 2015 Jun;83:373-9. doi: 10.1016/j.freeradbiomed.2015.01.025., Epub 2015 Feb 2. PMID:25656995 doi:https://dx.doi.org/10.1016/j.freeradbiomed.2015.01.025
- ↑ Banmeyer I, Marchand C, Clippe A, Knoops B. Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide. FEBS Lett. 2005 Apr 25;579(11):2327-33. PMID:15848167 doi:https://dx.doi.org/10.1016/j.febslet.2005.03.027
- ↑ Fisher AB. Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A(2) activities. Antioxid Redox Signal. 2011 Aug 1;15(3):831-44. doi: 10.1089/ars.2010.3412. Epub , 2011 Mar 31. PMID:20919932 doi:https://dx.doi.org/10.1089/ars.2010.3412
- ↑ Noh DY, Ahn SJ, Lee RA, Kim SW, Park IA, Chae HZ. Overexpression of peroxiredoxin in human breast cancer. Anticancer Res. 2001 May-Jun;21(3B):2085-90. PMID:11497302
- ↑ Rafiei S, Tiedemann K, Tabaries S, Siegel PM, Komarova SV. Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis. Cancer Lett. 2015 Jun 1;361(2):262-70. doi: 10.1016/j.canlet.2015.03.012. Epub, 2015 Mar 14. PMID:25779674 doi:https://dx.doi.org/10.1016/j.canlet.2015.03.012
- ↑ Hirotsu S, Abe Y, Okada K, Nagahara N, Hori H, Nishino T, Hakoshima T. Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12333-8. PMID:10535922
