Structural insights into recognition of acetylated histone ligands by the BRPF1 bromodomain.

•Solved the crystal structure of the BRPF1 bromodomain bound to the H2AK5ac ligand.•Solved the crystal structure of the BRPF1 bromodomain bound to the H4K12ac ligand.•Site-directed mutagenesis identifies critical binding pocket residues.•ITC experiments quantified the effect mutations have on ligand binding affinity.•We outline the molecular mechanism of acetyllysine binding by the BRPF1 bromodomain.•Ordered water molecules are an essential component driving ligand recognition.