Significant perturbations in amide ( 1 H, 15 N) chemical shifts were apparent throughout the protein, including for several lid residues, upon titration (up to a ligand:protein molar ratio of 1.2:1) of AM-7209 into 50 µM WT MDM2 (Figure , and Figures ). When the same concentrations of AM-7209 were titrated into 50 µM I19G significant chemical shifts perturbations were observed throughout the protein with the crucial exception of lid residues (Figure ). Displaying the combined 1 H, N CSP values on a 3D structure of MDM2, confirms that the large perturbations observed in the lid region of WT MDM2 are absent in the case of the I19G mutant (Figure and). Figures show data for the entire protein sequences.