Peroxiredoxins in Parasites

Significance: Parasite survival and virulence relies on effective defenses against reactive oxygen and nitrogen species produced by the host immune system. Peroxiredoxins (Prxs) are ubiquitous enzymes now thought to be central to such defenses and, as such, have potential value as drug targets and vaccine antigens. Recent Advances: Plasmodial and kinetoplastid Prx systems are the most extensively studied, yet remain inadequately understood. For many other parasites our knowledge is even less well developed. Through parasite genome sequencing efforts, however, the key players are being discovered and characterized. Here we describe what is known about the biochemistry, regulation, and cell biology of Prxs in parasitic protozoa, helminths, and fungi. At least one Prx is found in each parasite with a sequenced genome, and a notable theme is the common patterns of expression, localization, and functionality among sequence-similar Prxs in related species. Critical Issues: The nomenclature of Prxs from parasites is in a state of disarray, causing confusion and making comparative inferences difficult. Here we introduce a systematic Prx naming convention that is consistent between organisms and informative about structural and evolutionary relationships. Future Directions: The new nomenclature should stimulate the crossfertilization of ideas among parasitologists and with the broader redox research community. The diverse parasite developmental stages and host environments present complex systems in which to explore the variety of roles played by Prxs, with a view toward parlaying what is learned into novel therapies and vaccines that are urgently needed. Antioxid. Redox Signal. 17, 608-633.Keywords: Entamoeba histolytica, Plasmodium falciparum, Alkyl hydroperoxide reductase, Falciparum 1 Cys Peroxiredoxin, Thiol specific antioxidant, One conserved cysteine, Protozoan trichomonas vaginalis, Amebic liver abscess, Schistosoma mansoni thioredoxin, Redox sensitive oligomerizatio

Fiction Fix 10

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Spelunking in Plato\u27s Cave

The following creative dissertation, Spelunking in Plato’s Cave, includes an analytical introduction, placing my work in conversation with other writers, followed by a collection of original short stories, loosely themed around illness, family dynamics, and philosophical allusions

Mapping the Active Site Helix-to-Strand Conversion of CxxxxC Peroxiredoxin Q Enzymes

Peroxiredoxins (Prx) make up a family of enzymes that reduce peroxides using a peroxidatic cysteine residue; among these, members of the PrxQ subfamily are proposed to be the most ancestral-like yet are among the least characterized. In many PrxQ enzymes, a second “resolving” cysteine is located five residues downstream from the peroxidatic Cys, and these residues form a disulfide during the catalytic cycle. Here, we describe three hyperthermophilic PrxQ crystal structures originally determined by the RIKEN structural genomics group. We reprocessed the diffraction data and conducted further refinement to yield models with <i>R</i>_free values lowered by 2.3–7.2% and resolution extended by 0.2–0.3 Å, making one, at 1.4 Å, one of the best resolved peroxiredoxins to date. Comparisons of two matched thiol and disulfide forms reveal that the active site conformational change required for disulfide formation involves a transition of ∼20 residues from a pair of α-helices to a β-hairpin and 3₁₀-helix. Each conformation has ∼10 residues with a high level of disorder providing slack that allows the dramatic shift, and the two conformations are anchored to the protein core by distinct nonpolar side chains that fill three hydrophobic pockets. Sequence conservation patterns confirm the importance of these and a few additional residues for function. From a broader perspective, this study raises the provocative question of how to make use of the valuable information in the Protein Data Bank generated by structural genomics projects but not described in the literature, perhaps remaining unrecognized and certainly underutilized