Spatial analysis of mutations in the crystal structure of FLT3. (A) Ribbon representation of the crystal structure of FLT3 (pdb code: 1RJB).²⁴  Residues highlighted by this study are indicated and are shown in “stick” representation. Y572 is at the N-terminal residue of the JM domain visible in the crystal structure. D835 and N841 are both in the activation loop. Significant structural elements are color-coded, with the N-terminal kinase domain in green, the C-terminal kinase domain in blue, the activation loop in orange, and the juxtamembrane (JM) domain in yellow. P-loop is indicated. (B) The hydrogen-bonding network surrounding N841. N841 is the key residue in an extensive hydrogen-bonding network incorporating R815 in the catalytic loop; D839, S840, and N841 in the activation loop; K853 in the end of the activation loop; N887 at the end of the F-helix; and 5 water molecules. The activation loop is shown in orange and the C-terminal kinase domain in blue. Residues are shown in stick representation with nitrogen atoms in blue, oxygen atoms in red, and carbon atoms the same color as the domain. Water molecules are represented as red spheres, and hydrogen bonds are shown as purple dotted lines with distances shown in angstroms (nanometers). Figures were made using SETOR.²⁵