Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity
Figure 2
The inactive-to-active state switch of KIT tyrosine kinase domain.
(a) The inactive auto-inhibited state with the A-loop and the JMR adjacent to the active site (1T45 [34] (c) and the active state with a solvent-exposed JMR and an extended A-loop conformation (1PKG [108]) with schematic representation of the secondary structures observed in the inactive and the active states. (b) The intermediate state, inactive not auto-inhibited, observed in KIT complex with imatinib (1T46 [34]). Protein surface of KIT (gray) with the A-loop (red) and the JMR (yellow) shown as cartoons. Imatinib is shown as sticks. The principal H-bonds stabilizing the β-sheets are shows by green doted lines. Positions of residues V560 and D816, if resolved, are indicated as balls. The catalytic residues, DFG, indicated as sticks are zoomed in the inserts.