Peroxiredoxins in Parasites

Gretes, Michael; Poole, Leslie B.; Karplus, P. Andrew

doi:10.1089/ars.2011.4404

Cited by 84 publications

(74 citation statements)

References 271 publications

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“…21 Thus, to assess the "sensitivity" of these plasmodial enzymes, studies are needed that define the rate of hyperoxidation as a function of H 2 O 2 concentration. As noted in our review, 3 as of yet no Plasmodial Prx is known to be sensitive, consistent with none of these organisms having the sulfiredoxin enzyme that has the physiological role of reactivating hyperoxidized Prxs.…”

Section: Features Of Prx1 Family Disulfide Bonds Are Not Unusualsupporting

confidence: 81%

“…According to a recent survey we completed, 3 all parasites that cause a significant burden of disease feature Prxs among their countermeasures against the host immune system, and these enzymes have been considered as potential targets for drug development. 4 As part of our survey, we found that the naming of many Prxs in various parasites was highly inconsistent, making comparisons difficult.…”

Section: Introductionmentioning

confidence: 99%

“…4 As part of our survey, we found that the naming of many Prxs in various parasites was highly inconsistent, making comparisons difficult. To address this problem, we proposed a new nomenclature based on evolutionary relationships that assigns Prxs to one of five common subfamilies (Prx1, Prx6, Prx5, Tpx, PrxQ), 3 and we will use this nomenclature here.…”

Section: Introductionmentioning

confidence: 99%

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Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native “ball‐and‐socket” interacting residues by an affinity tag

Gretes

Karplus

2013

Protein Science

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Peroxiredoxins (Prxs) are ubiquitous and efficient antioxidant enzymes crucial for redox homeostasis in most organisms, and are of special importance for disease-causing parasites that must protect themselves against the oxidative weapons of the human immune system. Here, we describe reanalyses of crystal structures of two Prxs from malaria parasites. In addition to producing improved structures, we provide normalizing explanations for features that had been noted as unusual in the original report of these structures (Qiu et al., BMC Struct Biol 2012;12:2). Most importantly, we provide evidence that the unusual octameric assembly seen for Plasmodium yoelii Prx1a is not physiologically relevant, but arises because the structure is not of authentic P. yoelii Prx1a, but a variant we designate PyPrx1a N* that has seven native N-terminal residues replaced by an affinity tag. This N-terminal modification disrupts a previously unrecognized, hydrophobic "ball-and-socket" interaction conserved at the B-type dimer interface of Prx1 subfamily enzymes, and is accommodated by a fascinating two-residue "b-slip" type register shift in the b-strand association at a dimer interface. The resulting change in the geometry of the dimer provides a simple explanation for octamer formation. This study illustrates how substantive impacts can occur in protein variants in which native residues have been altered.

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Section: Features Of Prx1 Family Disulfide Bonds Are Not Unusualsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native “ball‐and‐socket” interacting residues by an affinity tag

Gretes

Karplus

2013

Protein Science

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“…These enzymes exist in almost all organisms (Chae et al, 1994;Robinson et al, 2010), and appear to be abundant in parasitic nematodes, with the ability to deoxidize H 2 O 2 into water in a system comprised by thioredoxin, thioredoxin reductase and NADPH (Chandrashekar et al, 2000;Henkle-Dührsen and Kampkötter, 2001). Although helminth TPXs have been extensively characterized (Gretes et al, 2012), limited information is available for Trichinella.…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of thioredoxin peroxidases from Trichinella spiralis

Zhang

Liu

et al. 2016

Veterinary Parasitology

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“…Leishmania infantum, an intracellular protozoan parasite with a digenetic life cycle (i.e., it shuttles between two hosts, insects and mammals), encodes several 2-Cys-Prxs (10)(11)(12), one of which is the mitochondrial homolog called mitochondrial tryparedoxin-peroxidase mTXNPx (13). We showed that mTXNPxdeficient promastigotes (i.e., the insect form) are significantly more sensitive to a temperature shift from 25°C to 37°C than promastigotes harboring functional mTXNPx (13).…”

mentioning

confidence: 99%

Mitochondrial peroxiredoxin functions as crucial chaperone reservoir inLeishmania infantum

Teixeira

Castro

Cruz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cytosolic eukaryotic 2-Cys-peroxiredoxins have been widely reported to act as dual-function proteins, either detoxifying reactive oxygen species or acting as chaperones to prevent protein aggregation. Several stimuli, including peroxide-mediated sulfinic acid formation at the active site cysteine, have been proposed to trigger the chaperone activity. However, the mechanism underlying this activation and the extent to which the chaperone function is crucial under physiological conditions in vivo remained unknown. Here we demonstrate that in the vector-borne protozoan parasite Leishmania infantum, mitochondrial peroxiredoxin (Prx) exerts intrinsic ATP-independent chaperone activity, protecting a wide variety of different proteins against heat stress-mediated unfolding in vitro and in vivo. Activation of the chaperone function appears to be induced by temperature-mediated restructuring of the reduced decamers, promoting binding of unfolding client proteins in the center of Prx's ringlike structure. Client proteins are maintained in a folding-competent conformation until restoration of nonstress conditions, upon which they are released and transferred to ATP-dependent chaperones for refolding. Interference with client binding impairs parasite infectivity, providing compelling evidence for the in vivo importance of Prx's chaperone function. Our results suggest that reduced Prx provides a mitochondrial chaperone reservoir, which allows L. infantum to deal successfully with protein unfolding conditions during the transition from insect to the mammalian hosts and to generate viable parasites capable of perpetuating infection.chaperone | Leishmania | peroxiredoxin

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Peroxiredoxins in Parasites

Cited by 84 publications

References 271 publications

Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native “ball‐and‐socket” interacting residues by an affinity tag

Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native “ball‐and‐socket” interacting residues by an affinity tag

Cloning and characterization of thioredoxin peroxidases from Trichinella spiralis

Mitochondrial peroxiredoxin functions as crucial chaperone reservoir inLeishmania infantum

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