Fig. 2.

Locations of mutations, inhibitors and the activation loop in ABL kinase. A) Spatial distribution of mutations in eight ABL-drug complexes. The shown structure is ABL kinase complexed with ATP (PDB ID: 2G1T). Mutations causing resistance (ΔΔG ≥ 1.36 Kcal/mol) to at least one drug are colored in red, other mutations (ΔΔG <1.36 Kcal/mol) are colored in blue, and ATP interacting residues are shown in the bottom right box. B) The conformations of type I and type II binding modes. Type I inhibitors (e.g., axitinib, in blue) bind to the active kinase, where the activation loop (A-Loop) adopts the DFG-in conformation (PDB ID: 4WA9). They occupy only the hinge region. Type II inhibitors (e.g., imatinib, in orange) bind to the inactive kinase, where the A-Loop adopts the DFG-out conformation (PDB ID: 1OPJ). They have extra access to the gatekeeper and back pocket. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)