ArticleScientific reports2019
Differential Inhibition of Human and Trypanosome Ubiquitin E1S by TAK-243 Offers Possibilities for Parasite Selective Inhibitors.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.PLoS neglected tropical diseases · 2024Pooled it
- From Epigenetic Regulation to Protein Degradation: Emerging Strategies for Anti-Infective Drug Discovery.International journal of molecular sciences · 2026Review
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Determination of key hub genes in Leishmaniasis as potential factors in diagnosis and treatment based on a bioinformatics study.Scientific reports · 2024Article
- Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.PLoS pathogens · 2024Article
- Unraveling the Mechanism of Action of Myricetin in the Inhibition of hUba1∼Ubiquitin Thioester Bond Formation viaACS omega · 2023Article
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery.ACS bio & med chem Au · 2023Review
- The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy.Frontiers in cellular and infection microbiology · 2022Review
- Leishmania differentiation requires ubiquitin conjugation mediated by a UBC2-UEV1 E2 complex.PLoS pathogens · 2020Article
- Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases.Frontiers in chemistry · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Novel strategies to target Trypanosoma brucei, Trypanosoma cruzi and Leishmania are urgently needed to generate better and safer drugs against Human African Trypanosomiasis, Chagas disease and Leishmaniasis, respectively. Here, we investigated the feasibility of selectively targeting in trypanosomatids the ubiquitin E1 activating enzyme (UBA1), an essential eukaryotic protein required for protein ubiquitination. Trypanosomatids contain two UBA1 genes in contrast to mammals and yeast that only have one, and using T. brucei as a model system, we show that both are active in vitro. Surprisingly, neither protein is inhibited by TAK-243, a potent inhibitor of human UBA1. This resistance stems from differences with the human protein at key amino acids, which includes a residue termed the gatekeeper because its mutation in E1s leads to resistance to TAK-243 and related compounds. Importantly, our results predict that trypanosomatid selective UBA1 inhibition is feasible and suggest ways to design novel compounds to achieve this.
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