Fig. 4.

Binding of conformation-selective ligands to apo SrcKD induces short and long-range dynamic changes. Backbone amide resonance intensity ratios of SrcKD ligand-bound states: a dasatinib, b DAS-DFGO2, c DAS-CHO2, relative to apo SrcKD were analyzed by histograms and by structure mapping (PDB-entry 3G5D, 4YBJ, 4YBK)^30,31 to infer dynamic changes. Intensity ratios >1 (sharpening) suggest increased fast internal motions relative to conformational exchange, intensity ratios <1 (broadening) suggest the opposite. Long-range sharpening occurs in the peptide binding interface upon dasatinib and DAS-DFGO2 binding but to a less extent for DAS-CHO2. In all states, broadening occurs in the SH3, SH2, Csk-binding interfaces but is most pronounced in the DAS-CHO2 bound state. Intensity ratios for the ligand-bound state to apo the state were determined only for resonances assigned and resolved in both states. IP error bars here and in subsequent IP figures are based on the S.D. of the noise level in the NMR spectra