ArticlePloS one2016
Segmental Isotope Labelling of an Individual Bromodomain of a Tandem Domain BRD4 Using Sortase A.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Bromodomain dimers: A case study of BRD4 and family-wide AlphaFold predictions.Structural dynamics (Melville, N.Y.) · 2026Article
- Segmental Isotope Labeling of the Prion Protein: Identification of a Key Residue for Copper-Mediated Interdomain Structure.ACS chemical biology · 2025Article
- Efficient Segmental Isotope Labeling of Integral Membrane Proteins for High-Resolution NMR Studies.Journal of the American Chemical Society · 2024Article
- Bromodomain Interactions with Acetylated Histone 4 Peptides in the BRD4 Tandem Domain: Effects on Domain Dynamics and Internal Flexibility.Biochemistry · 2022Article
- Sortase-mediated segmental labeling: A method for segmental assignment of intrinsically disordered regions in proteins.PloS one · 2021Article
- Quantifying the Selectivity of Protein-Protein and Small Molecule Interactions with Fluorinated Tandem Bromodomain Reader Proteins.ACS chemical biology · 2020Article
- Optimization of sortase A ligation for flexible engineering of complex protein systems.The Journal of biological chemistry · 2020Article
- NMR Structure and Dynamics of TonB Investigated by Scar-Less Segmental Isotopic Labeling Using a Salt-Inducible Split Intein.Frontiers in chemistry · 2020Article
- Broadening the scope of sortagging.RSC advances · 2019Review
- Natural Occurring and Engineered Enzymes for Peptide Ligation and Cyclization.Frontiers in chemistry · 2019Review
- Segmental isotopic labeling of HIV-1 capsid protein assemblies for solid state NMR.Journal of biomolecular NMR · 2018Article
- A molecular engineering toolbox for the structural biologist.Quarterly reviews of biophysics · 2017Review
- Potent and selective bivalent inhibitors of BET bromodomains.Nature chemical biology · 2016Article
- Recent advances in sortase-catalyzed ligation methodology.Current opinion in structural biology · 2016Review
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Authors and funding
4 authors.
Funding
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Abstract
Bromodomain and extra-terminal (BET) family of proteins are one of the major readers of epigenetic marks and an important target class in oncology and other disease areas. The importance of the BET family of proteins is manifested by the explosion in the number of inhibitors against these targets that have successfully entered clinical trials. One important BET family member is bromodomain containing protein 4 (BRD4). Structural and biophysical studies of BRD4 are complicated by its tertiary-structure consisting of two bromodomains connected by a flexible inter-domain linker of approximately 180 amino acids. A detailed understanding of the interplay of these bromodomains will be key to rational drug design in BRD4, yet there are no reported three-dimensional structures of the multi-domain BRD4 and NMR studies of the tandem domain are hampered by the size of the protein. Here, we present a method for rapid Sortase A-mediated segmental labelling of the individual bromodomains of BRD4 that provides a powerful strategy that will enable NMR studies of ligand-bromodomain interactions with atomic detail. In our labelling strategy, we have used U-[2H,15N]-isotope labelling on the C-terminal bromodomain with selective introduction of 13CH3 methyl groups on Ile (δ1), Val and Leu, whereas the N-terminal bromodomain remained unlabelled. This labelling scheme resulted in significantly simplified NMR spectra and will allow for high-resolution interaction, structure and dynamics studies in the presence of ligands.
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