ArticleExperimental parasitology2020
Evaluating the GCN5b bromodomain as a novel therapeutic target against the parasite Toxoplasma gondii.
Article in Experimental parasitology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Parasite-specific essential bromodomain protein TgBDP4 is a key epigenetic reader and a potential drug target for the parasite Toxoplasma gondii.The Journal of biological chemistry · 2026Article
- PfGCN5 is essential for Plasmodium falciparum survival and transmission and regulates Pf H2B.Z acetylation and chromatin structure.Nucleic acids research · 2025Article
- Acetylation-Mediated Epigenetic Consequences for Biological Control and Cancer.Results and problems in cell differentiation · 2025Review
- Identification of novel bromodomain inhibitors ofAntimicrobial agents and chemotherapy · 2024Article
- 1,3,4-oxadiazoles as inhibitors of the atypical member of the BET family bromodomain factor 3 fromFrontiers in microbiology · 2024Article
- Article
- Chemical Inhibition of Bromodomain Proteins in Insect-Stage African Trypanosomes Perturbs Silencing of the Variant Surface Glycoprotein Repertoire and Results in Widespread Changes in the Transcriptome.Microbiology spectrum · 2023Article
- Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- "Reading" a new chapter in protozoan parasite transcriptional regulation.PLoS pathogens · 2021Review
- Protein acetylation in the critical biological processes in protozoan parasites.Trends in parasitology · 2021Review
- Exploring the Histone Acetylation Cycle in the Protozoan ModelFrontiers in cell and developmental biology · 2020Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Toxoplasma gondii is a protozoan parasite of great importance in human and veterinary health. The frontline treatment of antifolates suffers a variety of drawbacks, including toxicity and allergic reactions, underscoring the need to identify novel drug targets for new therapeutics to be developed. We previously showed that the Toxoplasma lysine acetyltransferase (KAT) GCN5b is an essential chromatin remodeling enzyme in the parasite linked to the regulation of gene expression. We have previously established that the KAT domain is a liability that can be targeted in the parasite by compounds like garcinol; here, we investigate the potential of the bromodomain as a targetable element of GCN5b. Bromodomains bind acetylated lysine residues on histones, which helps stabilize the KAT complex at gene promoters. Using an inducible dominant-negative strategy, we found that the GCN5b bromodomain is critical for Toxoplasma viability. We also found that the GCN5-family bromodomain inhibitor, L-Moses, interferes with the ability of the GCN5b bromodomain to associate with acetylated histone residues using an in vitro binding assay. Moreover, L-Moses displays potent activity against Toxoplasma tachyzoites in vitro, which can be overcome if parasites are engineered to over-express GCN5b. Collectively, our data support the GCN5b bromodomain as an attractive target for the development of new therapeutics.
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