Photoreactive “Nanorulers” Detect a Novel Conformation of Full Length HDAC3-SMRT Complex in Solution

摘要: Histone deacetylase 3 (HDAC3) is a promising epigenetic drug target for multiple therapeutic applications. Direct interaction between the Deacetylase Activating Domain of silencing mediator retinoid or thyroid-hormone receptors (SMRT-DAD) required activation enzymatic activity HDAC3. The structure this complex and nature interactions with HDAC inhibitors in solution are unknown. Using novel photoreactive probes, “nanorulers”, we determined distance catalytic site full-length HDAC3 SMRT-DAD at physiologically relevant conditions found it to be substantially different from that predicted by X-ray model Δ379–428 aa truncated Further experiments indicated might change response chemical stimuli, while remained unaffected. These observations were further validated Saturation Transfer Difference (STD) NMR experiments. We propose observed changes ...