Profiling the dynamic interfaces of fluorinated transcription complexes for ligand discovery and characterization.

ABSTRACT: The conformationally dynamic binding surfaces of transcription complexes present a particular challenge for ligand discovery and characterization. In the case of the KIX domain of the master coactivator CBP/p300, few small molecules have been reported that target its two allosterically regulated binding sites despite the important roles that KIX plays in processes ranging from memory formation to hematopoiesis. Taking advantage of the enrichment of aromatic amino acids at protein interfaces, here we show that the incorporation of six (19)F-labeled aromatic side chains within the KIX domain enables recapitulation of the differential binding footprints of three natural activator peptides (MLL, c-Myb, and pKID) in complex with KIX and effectively reports on allosteric changes upon binding usi

SUBMITTER: Pomerantz WC 

PROVIDER: S-EPMC3423543 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature