ArticleThe Journal of biological chemistry2014
Structural and molecular basis of the peroxynitrite-mediated nitration and inactivation of Trypanosoma cruzi iron-superoxide dismutases (Fe-SODs) A and B: disparate susceptibilities due to the repair of Tyr35 radical by Cys83 in Fe-SODB through intramolecular electron transfer.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 60 citations in OpenAlex.
- Superoxide Dismutases in Immune Regulation and Infectious Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment.Parasites & vectors · 2022Article
- Mitochondrial CaAntioxidants & redox signaling · 2022Review
- Article
- Oxidative stress implications for therapeutic vaccine development against Chagas disease.Expert review of vaccines · 2021Review
- Repositioning of leishmanicidal [1,2,3]Triazolo[1,5-a]pyridinium salts for Chagas disease treatment: Trypanosoma cruzi cell death involving mitochondrial membrane depolarisation and Fe-SOD inhibition.Parasitology research · 2020Article
- Detection and quantification of nitric oxide-derived oxidants in biological systems.The Journal of biological chemistry · 2019Review
- Crystal structure of an iron superoxide dismutase from the pathogenic amoeba Acanthamoeba castellanii.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Cytosolic Fe-superoxide dismutase safeguardsProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Reactive species and pathogen antioxidant networks during phagocytosis.The Journal of experimental medicine · 2019Review
- Differential expression of proteins in genetically distinct Trypanosoma cruzi samples (TcI and TcII DTUs) isolated from chronic Chagas disease cardiac patients.Parasites & vectors · 2018Article
- Chemical Warfare at the Microorganismal Level: A Closer Look at the Superoxide Dismutase Enzymes of Pathogens.ACS infectious diseases · 2018Review
- Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine.Proceedings of the National Academy of Sciences of the United States of America · 2018Review
- Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration.Redox biology · 2018Review
- Proteomic analysis of serum deprivation in tongue squamous cell carcinoma.Molecular medicine reports · 2017Article
- Tyrosine-Nitrated Proteins: Proteomic and Bioanalytical Aspects.Antioxidants & redox signaling · 2017Review
- Kinetics, subcellular localization, and contribution to parasite virulence of aProceedings of the National Academy of Sciences of the United States of America · 2017Article
- TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice.Infection and immunity · 2016Article
- Antioxidant Systems are Regulated by Nitric Oxide-Mediated Post-translational Modifications (NO-PTMs).Frontiers in plant science · 2016Review
- Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress.PLoS neglected tropical diseases · 2016Article
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17 authors at 5 institutions in 3 countries.
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Abstract
Trypanosoma cruzi, the causative agent of Chagas disease, contains exclusively iron-dependent superoxide dismutases (Fe-SODs) located in different subcellular compartments. Peroxynitrite, a key cytotoxic and oxidizing effector biomolecule, reacted with T. cruzi mitochondrial (Fe-SODA) and cytosolic (Fe-SODB) SODs with second order rate constants of 4.6 ± 0.2 × 10(4) M(-1) s(-1) and 4.3 ± 0.4 × 10(4) M(-1) s(-1) at pH 7.4 and 37 °C, respectively. Both isoforms are dose-dependently nitrated and inactivated by peroxynitrite. Susceptibility of T. cruzi Fe-SODA toward peroxynitrite was similar to that reported previously for Escherichia coli Mn- and Fe-SODs and mammalian Mn-SOD, whereas Fe-SODB was exceptionally resistant to oxidant-mediated inactivation. We report mass spectrometry analysis indicating that peroxynitrite-mediated inactivation of T. cruzi Fe-SODs is due to the site-specific nitration of the critical and universally conserved Tyr(35). Searching for structural differences, the crystal structure of Fe-SODA was solved at 2.2 Å resolution. Structural analysis comparing both Fe-SOD isoforms reveals differences in key cysteines and tryptophan residues. Thiol alkylation of Fe-SODB cysteines made the enzyme more susceptible to peroxynitrite. In particular, Cys(83) mutation (C83S, absent in Fe-SODA) increased the Fe-SODB sensitivity toward peroxynitrite. Molecular dynamics, electron paramagnetic resonance, and immunospin trapping analysis revealed that Cys(83) present in Fe-SODB acts as an electron donor that repairs Tyr(35) radical via intramolecular electron transfer, preventing peroxynitrite-dependent nitration and consequent inactivation of Fe-SODB. Parasites exposed to exogenous or endogenous sources of peroxynitrite resulted in nitration and inactivation of Fe-SODA but not Fe-SODB, suggesting that these enzymes play distinctive biological roles during parasite infection of mammalian cells.
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