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.
BT - Journal of Medicinal Chemistry C1 - 0214 DA - 2016 Jun 09 DO - 10.1021/acs.jmedchem.6b00215 IS - 11 J2 - J. Med. Chem. LA - eng M3 - Research Article N2 -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.
PY - 2016 SE - 5555 SP - 5555 EP - 5561 T2 - Journal of Medicinal Chemistry TI - Twenty crystal structures of bromodomain and PHD finger containing protein 1 (BRPF1)/ligand complexes reveal conserved binding motifs and rare interactions VL - 59 SN - 1520-4804 ER -