Twenty crystal structures of bromodomain and PHD finger containing protein 1 (BRPF1)/ligand complexes reveal conserved binding motifs and rare interactions

TitleTwenty crystal structures of bromodomain and PHD finger containing protein 1 (BRPF1)/ligand complexes reveal conserved binding motifs and rare interactions
Publication TypeJournal Article
Year of Publication2016
AuthorsZhu J., Caflisch A.
JournalJournal of Medicinal Chemistry
Volume59
Start Page5555
Issue11
Pagination5555-5561
Date Published2016 Jun 09
Type of ArticleResearch Article
ISSN1520-4804
KeywordsAdaptor 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.

DOI10.1021/acs.jmedchem.6b00215
pubindex

0214

Alternate JournalJ. Med. Chem.
PubMed ID27167503
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