Fig. 1.

Src can adopt distinct conformations and integrates diverse inputs that regulate its kinase activity. a Distinct active and inactive conformations are induced when SrcKD binds to conformation-selective ligands. Dasatinib stabilizes the “DFG-Asp-in/αC-in” active conformation, whereas DAS-DFGO2, and DAS-CHO2, stabilize the “DFG-Asp-out/αC-in” and “DFG-Asp-in/αC-out” inactive conformations, respectively. b In Src, allosteric communication between the ATP-, substrate peptide-binding sites and the regulatory sites is propagated through an allosteric network (stick and surface representation) that was previously identified from MD simulations¹⁹. This network spans the kinase domain from the N-lobe to the C-lobe and includes catalytic and regulatory elements, and suggests a mechanism for integrating diverse regulatory input signals