Fig. 3: Structure of MITF and ligand identification by fragment-based NMR screening.
From: Fragment-based discovery enables direct targeting of the melanoma oncogene MITF
a Apo structure of MITF(217-296) lacking the basic region (PDB ID 4ATH) highlighting the small pocket, referred to as the kink pocket. The “site points”, shown in white, show the more buried part of the pocket. The three-residue insertion is shown in red. The kinked and straight helices are shown in green and cyan, respectively. b 19F NMR spectra from screening MITF(180-296) with the LEF4000 library. Spectra show a fragment mixture in the absence (black) or presence (red) of MITF. Hit 1 (near -123.5 ppm) is marked by the blue arrow. The signal near -112.5 ppm comes from a different fragment hit. c Validation of 1 by 1D protein observed NMR using MITF(180-296). d Validation of 1 by 2D 1H,13C-HMQC using MITF(217-296).
