Twenty crystal structures of bromodomain and PHD finger containing protein 1 (BRPF1)/ligand complexes reveal conserved binding motifs and rare interactions
Title | Twenty crystal structures of bromodomain and PHD finger containing protein 1 (BRPF1)/ligand complexes reveal conserved binding motifs and rare interactions |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Zhu J., Caflisch A. |
Journal | Journal of Medicinal Chemistry |
Volume | 59 |
Start Page | 5555 |
Issue | 11 |
Pagination | 5555-5561 |
Date Published | 2016 Jun 09 |
Type of Article | Research Article |
Keywords | Adaptor Proteins, Signal Transducing, Binding Sites, Crystallography, X-Ray, Humans, Ligands, Molecular Docking Simulation, Molecular Structure, Nuclear Proteins, Protein Domains, Protein Interaction Domains and Motifs, Water |
Abstract | BRPF1 plays a scaffolding role in transcription. We report on fragment screening by high-throughput docking to the BRPF1 bromodomain which resulted in six chemotypes with very favorable ligand efficiency (0.45-0.50 kcal/mol per non-hydrogen atom). Twenty crystal structures of BRPF1/ligand complexes show structural conservation in the acetyllysine binding site, common binding motifs, and unusual interactions (e.g., the replacement of a conserved water molecule). The structural information is useful for the design of chemical probes. |
DOI | 10.1021/acs.jmedchem.6b00215 |
pubindex | 0214 |
Alternate Journal | J. Med. Chem. |
PubMed ID | 27167503 |
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