The Peroxiredoxin Repair Proteins

Center for Structural Biology, Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Sub-cellular biochemistry 02/2007; 44:115-41. DOI: 10.1007/978-1-4020-6051-9_6
Source: PubMed


Sulfiredoxin and sestrin are cysteine sulfinic acid reductases that selectively reduce or repair the hyperoxidized forms of typical 2-Cys peroxiredoxins within eukaryotes. As such these enzymes play key roles in the modulation of peroxide-mediated cell signaling and cellular defense mechanisms. The unique structure of sulfiredoxin facilitates access to the peroxiredoxin active site and novel sulfur chemistry.

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    • "The mature Srx has a catalytic cysteine (Cys72) involved in the activity. Plant Srxs have an additional non-catalytic cysteine (Cys88; Iglesias-Baena et al., 2010) and, similar to mammalian Srxs, display low efficiency as retroreducing enzymes (Jönsson and Lowther, 2007). Unlike human Srx, only able to retroreduce typical 2-Cys-Prx, AtSrx has a lower substrate specificity showing activity toward typical and atypical Prxs, in different cellular compartments and in different organisms. "
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    ABSTRACT: Mitochondrial respiration provides the energy needed to drive metabolic and transport processes in cells. Mitochondria are a significant site of reactive oxygen species (ROS) production in plant cells, and redox-system components obey fine regulation mechanisms that are essential in protecting the mitochondrial integrity. In addition to ROS, there are compelling indications that nitric oxide can be generated in this organelle by both reductive and oxidative pathways. ROS and reactive nitrogen species play a key role in signaling but they can also be deleterious via oxidation of macromolecules. The high production of ROS obligates mitochondria to be provided with a set of ROS scavenging mechanisms. The first line of mitochondrial antioxidants is composed of superoxide dismutase and the enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge ROS but also to repair cell damage and possibly serve as redox sensors. The dithiol-disulfide exchanges form independent signaling nodes and act as antioxidant defense mechanisms as well as sensor proteins modulating redox signaling during development and stress adaptation. The presence of thioredoxin (Trx), peroxiredoxin (Prx) and sulfiredoxin (Srx) in the mitochondria has been recently reported. Cumulative results obtained from studies in salt stress models have demonstrated that these redox proteins play a significant role in the establishment of salt tolerance. The Trx/Prx/Srx system may be subjected to a fine regulated mechanism involving post-translational modifications, among which S-glutathionylation and S-nitrosylation seem to exhibit a critical role that is just beginning to be understood. This review summarizes our current knowledge in antioxidative systems in plant mitochondria, their interrelationships, mechanisms of compensation and some unresolved questions, with special focus on their response to abiotic stress.
    Full-text · Article · Nov 2013 · Frontiers in Plant Science
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    • "In prokaryotes, Prxs are thought to be required only for ROS detoxification purposes (Wood et al., 2003). It has therefore been assumed that bacteria do not contain any active Srxs (Biteau et al., 2003; Findlay et al., 2005; Jonsson & Lowther, 2007). However, it was recently reported that 2-Cys Prxs from the cyanobacteria "
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    ABSTRACT: The overoxidation of 2-Cys peroxiredoxins (Prxs) into a sulfinic form was thought to be an irreversible protein inactivation process until sulfiredoxins (Srxs) were discovered. These are enzymes occurring among eukaryotes, which are able to reduce sulfinylated Prxs. Although Prxs are present in the three domains of life, their reduction by Srxs has been described only in eukaryotes so far. Here it was established that the cyanobacterium Anabaena PCC 7120 has a Srx homologue (SrxA), which is able to specifically reduce the sulfinic form of the 2-Cys Prx (PrxA) both in vivo and in vitro. A mutant lacking the srxA gene was found to be more sensitive than the wild type to oxidative stress. Sulfiredoxin homologues are restricted to the cyanobacterial and eukaryotic genomes sequenced so far. The present phylogenetic analysis of Srx and 2-Cys Prx sequences showed a pattern of coevolution of the enzyme and its substrate that must have involved an ancient gene transfer between ancestors of Cyanobacteria and Eukaryotes, followed by a more recent transfer from Cyanobacteria to Plantae through the chloroplastic endosymbiosis. This is the first functional characterization of a Srx enzyme in a prokaryotic organism.
    Full-text · Article · Jun 2011 · New Phytologist
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    • "The role of sestrin 2 as a sulfinyl reductase is a controversial issue [16] [17], but sestrin 2 has been shown to partially mediate protection by NO • against Prx overoxidation [18]. Nonetheless, Srx is largely acknowledged as the " Prx repair enzyme " that helps keep 2-Cys Prx's active by reducing the overoxidized (inactive) forms [19] [20]. Interestingly, Srx reduces sulfinic cytosolic Prx's 1 and 2 as well as mitochondrial Prx 3, with subsequent cellular resistance to apoptosis [21]. "
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    ABSTRACT: Peroxiredoxins (Prx's) are a family of peroxidases that maintain thiol homeostasis by catalyzing the reduction of organic hydroperoxides, H₂O₂, and peroxynitrite. Under conditions of oxidative stress, eukaryotic Prx's can be inactivated by the substrate-dependent oxidation of the catalytic cysteine to sulfinic acid, which may regulate the intracellular messenger function of H₂O₂. A small redox protein, sulfiredoxin (Srx), conserved only in eukaryotes, has been shown to reduce sulfinylated 2-Cys Prx's, adding to the complexity of the H₂O₂ signaling network. In this study, we addressed the regulation of Srx expression in immunostimulated primary macrophages that produce both reactive oxygen species (ROS) and nitric oxide (NO(•)). We present genetic evidence that NO-mediated Srx up-regulation is mediated by the transcription factor nuclear factor erythroid 2-related factor (Nrf2). We also show that the NO(•)/Srx pathway inhibits generation of ROS. These results reveal a link between innate immunity and H₂O₂ signaling. We propose that an NO(•)/Nrf2/Srx pathway participates in the maintenance of redox homeostasis in cytokine-activated macrophages and other inflammatory settings.
    Full-text · Article · Apr 2011 · Free Radical Biology and Medicine
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