ArticleThe Journal of experimental medicine2002
A key role for old yellow enzyme in the metabolism of drugs by Trypanosoma cruzi.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Trypanocidal drugs for late-stage, symptomatic Chagas disease (Trypanosoma cruzi infection).The Cochrane database of systematic reviews · 2020Pooled it
- Structural and evolutionary dissection of NADPH-binding motifs in NADPH-preferring ene-reductases.Protein science : a publication of the Protein Society · 2026Article
- Expression Analysis of Thirteen Genes in Response to Nifurtimox and Benznidazole in Mexican Isolates of Trypanosoma cruzi by Digital PCR.Acta parasitologica · 2025Article
- Gut Bacteria Encode Reductases that Biotransform Steroid Hormones.bioRxiv : the preprint server for biology · 2024Article
- Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- A Data-Driven Approach to Construct a Molecular Map ofVaccines · 2023Article
- New Insights into the Role of thePathogens (Basel, Switzerland) · 2023Article
- Molecular Characterization of Four Mexican Isolates of Trypanosoma cruzi and Their Profile Susceptibility to Nifurtimox.Acta parasitologica · 2022Article
- Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi.PLoS neglected tropical diseases · 2022Article
- Lipid droplets of protozoan parasites: survival and pathogenicity.Memorias do Instituto Oswaldo Cruz · 2022Article
- Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases.RSC medicinal chemistry · 2020Review
- Co-opting oxylipin signals in microbial disease.Cellular microbiology · 2019Review
- A role for trypanosomatid aldo-keto reductases in methylglyoxal, prostaglandin and isoprostane metabolism.The Biochemical journal · 2018Article
- Cloning and characterization of enoate reductase with high β-ionone to dihydro-β-ionone bioconversion productivity.BMC biotechnology · 2018Article
- Endogenous overexpression of an active phosphorylated form of DNA polymerase β under oxidative stress in Trypanosoma cruzi.PLoS neglected tropical diseases · 2018Article
- Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical isolates.PloS one · 2018Article
- Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism.Frontiers in microbiology · 2018Review
- Old Yellow Enzyme fromFrontiers in immunology · 2018Article
- Article
- Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control.Frontiers in microbiology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma cruzi is the etiological agent of Chagas' disease. So far, first choice anti-chagasic drugs in use have been shown to have undesirable side effects in addition to the emergence of parasite resistance and the lack of prospect for vaccine against T. cruzi infection. Thus, the isolation and characterization of molecules essential in parasite metabolism of the anti-chagasic drugs are fundamental for the development of new strategies for rational drug design and/or the improvement of the current chemotherapy. While searching for a prostaglandin (PG) F(2alpha) synthase homologue, we have identified a novel "old yellow enzyme" from T. cruzi (TcOYE), cloned its cDNA, and overexpressed the recombinant enzyme. Here, we show that TcOYE reduced 9,11-endoperoxide PGH(2) to PGF(2alpha) as well as a variety of trypanocidal drugs. By electron spin resonance experiments, we found that TcOYE specifically catalyzed one-electron reduction of menadione and beta-lapachone to semiquinone-free radicals with concomitant generation of superoxide radical anions, while catalyzing solely the two-electron reduction of nifurtimox and 4-nitroquinoline-N-oxide drugs without free radical production. Interestingly, immunoprecipitation experiments revealed that anti-TcOYE polyclonal antibody abolished major reductase activities of the lysates toward these drugs, identifying TcOYE as a key drug-metabolizing enzyme by which quinone drugs have their mechanism of action.
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