ArticleMolecular and biochemical parasitology2010
Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi.
Article in Molecular and biochemical parasitology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 60 citations in OpenAlex.
- Ruthenium Complexes Containing Thiobenzamide Act as Potent and Selective Anti-ACS infectious diseases · 2026Article
- Comparative metabolism of conjugated and unconjugated pterins in Crithidia, Leishmania and African trypanosomes.PLoS neglected tropical diseases · 2025Article
- Targeting Trypanothione Metabolism in Trypanosomatids.Molecules (Basel, Switzerland) · 2024Review
- Epigallocathechin-Frontiers in cellular and infection microbiology · 2021Article
- Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning.International journal of molecular sciences · 2020Article
- Spiro-containing derivatives show antiparasitic activity against Trypanosoma brucei through inhibition of the trypanothione reductase enzyme.PLoS neglected tropical diseases · 2020Article
- Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases.Molecules (Basel, Switzerland) · 2020Review
- Natural Sesquiterpene Lactones of the 4,15-Molecules (Basel, Switzerland) · 2019Article
- Understanding the Cross-Talk of Redox Metabolism and Fe-S Cluster Biogenesis in Leishmania Through Systems Biology Approach.Frontiers in cellular and infection microbiology · 2019Article
- The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids.Pathogens (Basel, Switzerland) · 2018Review
- Identification of potential trypanothione reductase inhibitors among commercially available β-carboline derivatives using chemical space, lead-like and drug-like filters, pharmacophore models and molecular docking.Molecular diversity · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Glutathione reductase a unique enzyme: molecular cloning, expression and biochemical characterization from the stress adapted C4 plant, Pennisetum glaucum (L.) R. Br.Molecular biology reports · 2015Article
- Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect-stage Trypanosoma brucei.Molecular microbiology · 2015Article
- New drug target in protozoan parasites: the role of thioredoxin reductase.Frontiers in microbiology · 2015Review
- Trypanothione reductase: a target protein for a combined in vitro and in silico screening approach.PLoS neglected tropical diseases · 2015Article
- Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recover virulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy.Molecular microbiology · 2013Article
- Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei.The Journal of biological chemistry · 2013Article
- Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography.Journal of medicinal chemistry · 2011Article
- Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities.The Biochemical journal · 2011Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
As part of a drug discovery programme to discover new treatments for human African trypanosomiasis, recombinant trypanothione reductase from Trypanosoma brucei has been expressed, purified and characterized. The crystal structure was solved by molecular replacement to a resolution of 2.3A and found to be nearly identical to the T. cruzi enzyme (root mean square deviation 0.6A over 482 Calpha atoms). Kinetically, the K(m) for trypanothione disulphide for the T. brucei enzyme was 4.4-fold lower than for T. cruzi measured by either direct (NADPH oxidation) or DTNB-coupled assay. The K(m) for NADPH for the T. brucei enzyme was found to be 0.77microM using an NADPH-regenerating system coupled to reduction of DTNB. Both enzymes were assayed for inhibition at their respective S=K(m) values for trypanothione disulphide using a range of chemotypes, including CNS-active drugs such as clomipramine, trifluoperazine, thioridazine and citalopram. The relative IC(50) values for the two enzymes were found to vary by no more than 3-fold. Thus trypanothione reductases from these species are highly similar in all aspects, indicating that they may be used interchangeably for structure-based inhibitor design and high-throughput screening.
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Registered trials
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