FKBP12 in complex with bifunctional ligand a1d and the first bromodomain of BRD4

Non-catalytic heterobifunctional molecules promise to expand the range of therapeutic options by establishing complexes between key target proteins and presenter with additional functions. Here, we present the structure of a bifunctional ligand which induces a ternary complex with the immunophilin FKBP12 and the first bromodomain of the transcriptional regulator BRD4. The complex structure has been solved at a resolution of 1.8A.

非催化型双功能杂合分子可通过在关键靶蛋白与具备附加功能的呈递蛋白之间构建复合物，有望拓展治疗选择的范畴。本研究报道了一种双功能配体的结构，该配体可诱导形成包含亲免蛋白FKBP12与转录调节因子BRD4首个溴结构域（bromodomain）的三元复合物。该复合物结构以1.8埃（Å）的分辨率解析获得。