Peroxiredoxin 6: a bifunctional enzyme with glutathione peroxidase and phospholipase A₂ activities.
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TLDR
Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family and has important roles in both antioxidant defense and homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipids synthesis.Abstract:
Peroxiredoxin 6 (Prdx6) is the prototype and the only mammalian 1-Cys member of the Prdx family. Major differences from 2-Cys Prdxs include the use of glutathione (GSH) instead of thioredoxin as the physiological reductant, heterodimerization with πGSH S-transferase as part of the catalytic cycle, and the ability either to reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (phospholipase A(2) [PLA(2)] activity). The bifunctional protein has separate active sites for peroxidase (C47, R132, H39) and PLA(2) (S32, D140, H26) activities. These activities are dependent on binding of the protein to phospholipids at acidic pH and to oxidized phospholipids at cytosolic pH. Prdx6 can be phosphorylated by MAP kinases at T177, which markedly increases its PLA(2) activity and broadens its pH-activity spectrum. Prdx6 is primarily cytosolic but also is targeted to acidic organelles (lysosomes, lamellar bodies) by a specific targeting sequence (amino acids 31-40). Oxidant stress and keratinocyte growth factor are potent regulators of Prdx6 gene expression. Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis.read more
Citations
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Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling.
Eva-Maria Hanschmann,José R. Godoy,Carsten Berndt,Christoph Hudemann,Christopher Horst Lillig +4 more
TL;DR: This review summarizes the almost 50 years of research on these proteins, focusing primarily on data from vertebrates and mammals, that is, their potential impact and functions in different cell types, tissues, and various pathological conditions.
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Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides
TL;DR: Peroxiredoxins contain an active site cysteine that is sensitive to oxidation by H2O2, and Regulation of Prx via phosphorylation in response to extracellular signals allows the local accumulation of H2 O2 and thereby enables its messenger function.
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Redox regulation of mitochondrial function.
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References
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Characterization of a Mammalian Peroxiredoxin That Contains One Conserved Cysteine
TL;DR: Recombinant human 1-Cys Prx expressed in and purified from Escherichia coli has now been shown to reduce H2O2 with electrons provided by dithiothreitol and the enzyme represents a new type of peroxidase.
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1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities.
TL;DR: The results suggest that Ser32 in the GDSWG consensus sequence provides the catalytic nucleophile for the hydrolase activity of aiPLA2, while Cys47 in the PVCTTE consensus sequence is at the active site for peroxidase activity.
Journal ArticleDOI
Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism.
Yefim Manevich,Aron B. Fisher +1 more
TL;DR: It is postulate that Prdx6 functions in antioxidant defense mainly by facilitating repair of damaged cell membranes via reduction of peroxidized phospholipids via reduction with GSH to complete the enzymatic cycle.
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Crystal structure of a novel human peroxidase enzyme at 2.0 Å, resolution
TL;DR: The crystal structure of a human Prx enzyme, HORF6, reveals that the protein contains two discrete domains and forms a dimer, which accounts for the peroxidase activity of the enzyme, which contains no redox cofactors.
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Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with πGST
TL;DR: A physiological mechanism for glutathionylation of the oxidized catalytic cysteine of 1-cysPrx is indicated by its heterodimerization with pi GST followed by its GSH-mediated reduction and enzyme activation.
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Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism.
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