A5050532378- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Trypanosoma species research and implications
- Histone Deacetylase Inhibitors Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Research on Leishmaniasis Studies
- interferon and immune responses
- Insect Resistance and Genetics
- Phytoplasmas and Hemiptera pathogens
- Plant Virus Research Studies
- Multiple Myeloma Research and Treatments
University of Oxford
2018-2022
CREBBP (CBP/KAT3A) and its paralogue EP300 (KAT3B) are lysine acetyltransferases (KATs) that essential for human development. They each comprise 10 domains through which they interact with >400 proteins, making them important transcriptional co-activators key nodes in the protein-protein interactome. The bromodomains of enable binding acetylated residues from histones a number other including p53, p73, E2F, GATA1. Here, we report work to develop high-affinity, small-molecule ligand...
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents treating a range cancers inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET ligand (OXFBD02) inhibits interactions BRD4(1) with RelA subunit NF-κB, in addition to histone H4. This shows promising profile screen NCI-60 panel but was rapidly metabolised (t
The Trypanosoma cruzi (T. cruzi) parasite is the cause of Chagas disease, a neglected disease endemic in South America. life cycle T. complex and includes transitions between distinct stages. This change phenotype (without genotype) could be controlled by epigenetic regulation, might involve bromodomain-containing factors 1-5 (TcBDF1-5). However, little known about function TcBDF1-5. Here we describe fragment-based approach to identify ligands for factor 3 (TcBDF3). We expressed soluble...
TRIM33 is a member of the tripartite motif (TRIM) family proteins, some which possess E3 ligase activity and are involved in ubiquitin-dependent degradation proteins. Four TRIM TRIM24 (TIF1α), TRIM28 (TIF1β), (TIF1γ) TRIM66, contain C-terminal plant homeodomain (PHD) bromodomain (BRD) modules, bind to methylated lysine (KMen) acetylated (KAc), respectively. Here we investigate differences between two isoforms TRIM33, TRIM33α TRIM33β, using structural biophysical approaches. We show that...
CREBBP (CBP or KAT3A) and its paralogue P300 (also KAT3B) are lysine acetyltransferases (KATs) that essential for human development. They each comprise ten domains through which they interact with over 400 proteins, making them important transcriptional co-activators, key nodes in the protein-protein interactome. The bromodomain of enables binding acetylated residues from histones, a number other including p53, p73, E2F GATA1. Here we report work to develop high affinity, small molecule,...
<p>CREBBP (CBP or KAT3A) and its paralogue P300 (also KAT3B) are lysine acetyltransferases (KATs) that essential for human development. They each comprise ten domains through which they interact with over 400 proteins, making them important transcriptional co-activators, key nodes in the protein-protein interactome. The bromodomain of CREBBP enables binding acetylated residues from histones, a number other including p53, p73, E2F GATA1. Here we report work to develop high affinity,...
The Trypanosoma cruzi ( T. ) parasite is the cause of Chagas disease, a neglected disease endemic in South America. life cycle complex and includes transitions between distinct stages. This change phenotype (without genotype) could be controlled by epigenetic regulation, might involve bromodomain-containing factors 1-5 Tc BDF1-5). However, little known about function BDF1-5. Here we describe fragment-based approach to identify ligands for factor 3 BDF3). We expressed soluble construct BDF3...
The <i>Trypanosoma cruzi</i> (<i>T. cruzi</i>) parasite is the cause of Chagas disease, a neglected disease endemic in South America. life cycle <i>T. complex and includes transitions between distinct stages. This change phenotype (without genotype) could be controlled by epigenetic regulation, might involve bromodomain-containing factors 1-5 (<i>Tc</i>BDF1-5). However, little known about function <i>Tc</i>BDF1-5. Here we describe...
TRIM33 is a member of the tripartite motif (TRIM) family proteins, some which possess E3 ligase activity and are involved in ubiquitin-dependent degradation proteins. Four TRIM TRIM24 (TIF1α), TRIM28 (TIF1β), (TIF1γ) TRIM66, contain C-terminal plant homeodomain (PHD) bromodomain (BRD) modules, bind to methylated lysine (KMen) acetylated (KAc), respectively. Here we investigate differences between two isoforms TRIM33, TRIM33α TRIM33β using structural biophysical approaches. We show that N1039...