Anna K. Mapp

Transcriptional coactivators and their partner transcription factors play central roles in human disease yet are viewed as undruggable. Mapp has conducted comprehensive studies of divergent transcriptional coactivators to reveal mechanistic commonalities for complex formation with transcription factors. These insights include a shared flexible substructure critical for the conformational transitions needed to engage diverse binding partners and for allosteric communication. She demonstrated that these conformationally mobile regions comprise the optimal small-molecule binding sites, facilitating both allosteric and orthosteric regulation of transcription factor-coactivator complexes. This conceptual framework is extendable beyond transcription factor-coactivator complexes, moving intrinsically disordered protein-protein interaction (PPI) networks into the druggable realm.