Bromodomains are involved in the regulation of chromatin architecture and
transcription through the recognition of acetylated lysines in histones and
other proteins. Many of them are considered to be relevant pharmacological
targets for different pathologies. Three crystallographic structures of the
N-terminal bromodomain of BRD4 in complex with low-molecular-weight fragments
are presented. They show that similar molecules mimicking acetylated lysine bind
the bromodomain with different orientations and exploit different interactions.
It is also advised to avoid DMSO when searching for low-affinity fragments that
interact with bromodomains since DMSO binds in the acetylated lysine-recognition
pocket of BRD4.
