PrxQ B from Mycobacterium tuberculosis is a monomeric, thioredoxin-dependent and highly efficient fatty acid hydroperoxide reductase

Reyes, Aníbal M.; Vazquez, Diego S.; Zeida, Ari; Hugo, Martín; Piñeyro, María Dolores; Armas, María Inés De; Estrin, Darı́o A.; Radí, Rafael; Santos, Javier; Trujillo, Madia

doi:10.1016/j.freeradbiomed.2016.10.005

Cited by 21 publications

(23 citation statements)

References 75 publications

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“…glutamicum PrxQ mainly exists in monomer both under reduced and oxidized states, similar to polpar PrxQ and M . Tuberculosis PrxQ B [ 29 – 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Apart from H 2 O 2 , CHP, and t -BOOH, peroxynitrite has also been reported for the oxidizing substrate of M . tuberculosis PrxQ B [ 30 ]. Peroxynitrite was formed in vivo from the diffusion-controlled reaction between NO and O 2 •−, and has been implicated in promoting the development of various pathologies [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

“…The slope of the plot of k obs vs PrxQ concentration showed that the rate constant of the reduction of peroxynitrite by PrxQ was of (1.3 ± 0.4)×10 6 M −1 · s −1 at pH 7.4 and 25°C, similar to the result of Reyes et al reported for M . tuberculosis PrxQ B (1.4 ± 0.3 ×10 6 M −1 · s −1 at pH 7.4 and 25°C)[ 30 ]. Together, the preferred substrate of C .…”

Section: Resultsmentioning

confidence: 99%

“…Although PrxQs had been investigated in many organisms, much less is known about its physiologic and biochemical role in protecting C . glutamicum from peroxide toxicity [ 15 – 18 , 22 – 30 ]. Therefore, this study was performed to determine whether C .…”

Section: Introductionmentioning

confidence: 99%

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A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress

Zhao

et al. 2018

PLoS ONE

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Peroxiredoxin Q (PrxQ) that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx)/thioredoxin reductase (TrxR) system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP). Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

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“…glutamicum PrxQ mainly exists in monomer both under reduced and oxidized states, similar to polpar PrxQ and M . Tuberculosis PrxQ B [ 29 – 30 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress

Zhao

et al. 2018

PLoS ONE

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“…It has been shown that over-expression of TPx-Qs can cope with oxidative stresses in cyanobacteria. TPx-Q B from Mycobacterium tuberculosis is monomeric under reduced and oxidized states, and it is a thioredoxin-dependent and highly efficient fatty acid hydroperoxide reductase (33). Regardless of the mode of classification of these proteins, the catalytic mechanism of the enzyme remains central and relies on the redox-active cys, which is highly conserved in its amino acid sequence (34).…”

Section: Introductionmentioning

confidence: 99%

A Novel Thioredoxin-Dependent Peroxiredoxin (TPx-Q) Plays an Important Role in Defense Against Oxidative Stress and Is a Possible Drug Target in Babesia microti

et al. 2020

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Tyrosine substitution of a conserved active‐site histidine residue activates Plasmodium falciparum peroxiredoxin 6

et al. 2018

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Peroxiredoxins efficiently remove hydroperoxides and peroxynitrite in pro- and eukaryotes. However, isoforms of one subfamily of peroxiredoxins, the so-called Prx6-type enzymes, usually have very low activities in standard peroxidase assays in vitro. In contrast to other peroxiredoxins, Prx6 homologues share a conserved histidyl residue at the bottom of the active site. Here we addressed the role of this histidyl residue for redox catalysis using the Plasmodium falciparum homologue PfPrx6 as a model enzyme. Steady-state kinetics with tert-butyl hydroperoxide (tBuOOH) revealed that the histidyl residue is nonessential for Prx6 catalysis and that a replacement with tyrosine can even increase the enzyme activity four- to six-fold in vitro. Stopped-flow kinetics with reduced PfPrx6 , PfPrx6 , and PfPrx6 revealed a preference for H O as an oxidant with second order rate constants for H O and tBuOOH around 2.5 × 10 M s and 3 × 10 M s , respectively. Differences between the oxidation kinetics of PfPrx6 , PfPrx6 , and PfPrx6 were observed during a slower second-reaction phase. Our kinetic data support the interpretation that the reductive half-reaction is the rate-limiting step for PfPrx6 catalysis in steady-state measurements. Whether the increased activity of PfPrx6 is caused by a facilitated enzyme reduction because of a destabilization of the fully folded enzyme conformation remains to be analyzed. In summary, the conserved histidyl residue of Prx6-type enzymes is non-essential for catalysis, PfPrx6 is rapidly oxidized by hydroperoxides, and the gain-of-function mutant PfPrx6 might provide a valuable tool to address the influence of conformational changes on the reactivity of Prx6 homologues.

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PrxQ B from Mycobacterium tuberculosis is a monomeric, thioredoxin-dependent and highly efficient fatty acid hydroperoxide reductase

Cited by 21 publications

References 75 publications

A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress

A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress

A Novel Thioredoxin-Dependent Peroxiredoxin (TPx-Q) Plays an Important Role in Defense Against Oxidative Stress and Is a Possible Drug Target in Babesia microti

Tyrosine substitution of a conserved active‐site histidine residue activates Plasmodium falciparum peroxiredoxin 6

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