Fig. 3.

Binding of conformation-selective ligands to apo SrcKD induces CSP near the ATP-binding site and at select C-lobe residues. CSPs induced in SrcKD upon binding: a dasatinib, b DAS-DFGO2, c DAS-CHO2, were analyzed by histograms and by CSP mapping to their structures (PDB-entry 3G5D, 4YBJ, 4YBK)^30,31. Large CSPs occur predominantly around the inhibitors binding site in the active site cleft. Some residues within the C-lobe exhibit moderate CSPs suggesting that long-range allosteric effects are propagated. In the upper histogram panels, pep denotes peptide and BI denotes binding interface. Secondary structure elements β6 and β9 are absent in the structures here and in subsequent figures when the activation loop is disordered. The yellow, orange, and red histogram dashed lines here and in subsequent CSP figures indicate the magnitiude of the CSPs corresponding to the mean, 1 and 2 S.D. equal to or greater than the mean respectively