Twenty crystal structures of bromodomain and phd finger containing protein 1 (brpf1)/ligand complexes reveal conserved binding motifs and rare interactions.
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.
