ArticleThe Journal of biological chemistry2013
Molecular basis for the resistance of human mitochondrial 2-Cys peroxiredoxin 3 to hyperoxidation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Mechanism-based peroxiredoxin 3 inhibitors exploit a covalent warhead for cancer therapy.Science advances · 2025Article
- Peroxiredoxins-The Underrated Actors during Virus-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
- Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State.Antioxidants (Basel, Switzerland) · 2021Article
- Peroxiredoxins wear many hats: Factors that fashion their peroxide sensing personalities.Redox biology · 2021Review
- Unique Cellular and Biochemical Features of Human Mitochondrial Peroxiredoxin 3 Establish the Molecular Basis for Its Specific Reaction with Thiostrepton.Antioxidants (Basel, Switzerland) · 2021Article
- Discovery of Spilanthol Endoperoxide as a Redox Natural Compound Active against Mammalian Prx3 andAntioxidants (Basel, Switzerland) · 2020Article
- The mitochondrial peroxiredoxin displays distinct roles in different developmental stages of African trypanosomes.Redox biology · 2020Article
- Dynamics of a Key Conformational Transition in the Mechanism of Peroxiredoxin Sulfinylation.ACS catalysis · 2020Article
- Redox requirements for ubiquitin-like urmylation of Ahp1, a 2-Cys peroxiredoxin from yeast.Redox biology · 2020Article
- Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193.Free radical biology & medicine · 2019Article
- Reactive oxygen species, aging and articular cartilage homeostasis.Free radical biology & medicine · 2019Review
- Mass Spectrometry in Advancement of Redox Precision Medicine.Advances in experimental medicine and biology · 2019Review
- Peroxiredoxins in Cancer and Response to Radiation Therapies.Antioxidants (Basel, Switzerland) · 2019Review
- Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2.Protein science : a publication of the Protein Society · 2019Article
- The Multifaceted Impact of Peroxiredoxins on Aging and Disease.Antioxidants & redox signaling · 2018Review
- Novel hyperoxidation resistance motifs in 2-Cys peroxiredoxins.The Journal of biological chemistry · 2018Article
- Cellular Timekeeping: It's Redox o'Clock.Cold Spring Harbor perspectives in biology · 2018Review
- Experimentally Dissecting the Origins of Peroxiredoxin Catalysis.Antioxidants & redox signaling · 2018Article
- Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels.Oxidative medicine and cellular longevity · 2018Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Peroxiredoxins (Prxs) detoxify peroxides and modulate H2O2-mediated cell signaling in normal and numerous pathophysiological contexts. The typical 2-Cys subclass of Prxs (human Prx1-4) utilizes a Cys sulfenic acid (Cys-SOH) intermediate and disulfide bond formation across two subunits during catalysis. During oxidative stress, however, the Cys-SOH moiety can react with H2O2 to form Cys sulfinic acid (Cys-SO2H), resulting in inactivation. The propensity to hyperoxidize varies greatly among human Prxs. Mitochondrial Prx3 is the most resistant to inactivation, but the molecular basis for this property is unknown. A panel of chimeras and Cys variants of Prx2 and Prx3 were treated with H2O2 and analyzed by rapid chemical quench and time-resolved electrospray ionization-TOF mass spectrometry. The latter utilized an on-line rapid-mixing setup to collect data on the low seconds time scale. These approaches enabled the first direct observation of the Cys-SOH intermediate and a putative Cys sulfenamide (Cys-SN) for Prx2 and Prx3 during catalysis. The substitution of C-terminal residues in Prx3, residues adjacent to the resolving Cys residue, resulted in a Prx2-like protein with increased sensitivity to hyperoxidation and decreased ability to form the intermolecular disulfide bond between subunits. The corresponding Prx2 chimera became more resistant to hyperoxidation. Taken together, the results of this study support that the kinetics of the Cys-SOH intermediate is key to determine the probability of hyperoxidation or disulfide formation. Given the oxidizing environment of the mitochondrion, it makes sense that Prx3 would favor disulfide bond formation as a protection mechanism against hyperoxidation and inactivation.
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