title: Twenty Crystal Structures of Bromodomain and PHD Finger Containing Protein 1 (BRPF1)/Ligand Complexes Reveal Conserved Binding Motifs and Rare Interactions.
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.
authors.affiliation: Department of Biochemistry, University of Zürich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, University of Zürich , Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000737:chemistry*; D000072417:Protein Domains; D054730:Protein Interaction Domains and Motifs; D014867:Water / Q000737:chemistry; D000092468:Bromodomain Containing Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D008024:Ligands; D009687:Nuclear Proteins; D014867:Water; C086011:BRPF1 protein, human; D000092468:Bromodomain Containing Proteins