ArticleProteins2019
Disulfide bridge formation influences ligand recognition by the ATAD2 bromodomain.
Article in Proteins, 2019. 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, 12 citations in OpenAlex.
- Breaking barriers: transitioning from X-ray crystallography to cryo-EM for structural studies.Acta crystallographica. Section D, Structural biology · 2026Article
- Engineering and Adapting Disulfide-Containing Proteins to Enable Intracellular Functionality.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Breaking Barriers: Transitioning from X-ray Crystallography to Cryo-EM for Structural Studies of ATAD2B.bioRxiv : the preprint server for biology · 2025Article
- ATPase family AAA domain-containing protein 2 (ATAD2): From an epigenetic modulator to cancer therapeutic target.Theranostics · 2023Review
- Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions.Journal of medicinal chemistry · 2022Article
- Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Cell and Tissue Structure, Function, and Phenotype.Results and problems in cell differentiation · 2022Review
- Functional Roles of Bromodomain Proteins in Cancer.Cancers · 2021Review
- AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors.European journal of medicinal chemistry · 2021Review
- Hitting a Moving Target: Simulation and Crystallography Study of ATAD2 Bromodomain Blockers.ACS medicinal chemistry letters · 2020Article
- The BRPF1 bromodomain is a molecular reader of di-acetyllysine.Current research in structural biology · 2020Article
- Predicted Configuration and Stability of the ATAD2/SOX10 Complex Using Molecular Dynamics Simulations.Cancer diagnosis & prognosisArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The ATPase family, AAA domain-containing protein 2 (ATAD2) has a C-terminal bromodomain, which functions as a chromatin reader domain recognizing acetylated lysine on the histone tails within the nucleosome. ATAD2 is overexpressed in many cancers and its expression is correlated with poor patient outcomes, making it an attractive therapeutic target and potential biomarker. We solved the crystal structure of the ATAD2 bromodomain and found that it contains a disulfide bridge near the base of the acetyllysine binding pocket (Cys1057-Cys1079). Site-directed mutagenesis revealed that removal of a free C-terminal cysteine (C1101) residue greatly improved the solubility of the ATAD2 bromodomain in vitro. Isothermal titration calorimetry experiments in combination with the Ellman's assay demonstrated that formation of an intramolecular disulfide bridge negatively impacts the ligand binding affinities and alters the thermodynamic parameters of the ATAD2 bromodomain interaction with a histone H4K5ac peptide as well as a small molecule bromodomain ligand. Molecular dynamics simulations indicate that the formation of the disulfide bridge in the ATAD2 bromodomain does not alter the structure of the folded state or flexibility of the acetyllysine binding pocket. However, consideration of this unique structural feature should be taken into account when examining ligand-binding affinity, or in the design of new bromodomain inhibitor compounds that interact with this acetyllysine reader module.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.