Structural mapping of JM point mutations. (Left) Ribbon model of the crystal structure of the FLT3 kinase domain (Protein Data Bank [PDB] accession no. 1RJB) with green activation loop and yellow JM domain. The positions of internal tandem duplications (ITDs) in JM-Z, leading to FLT3 activation, are indicated. ^*Some ITDs are found in the tyrosine kinase domain and are not indicated. (Right) Close view of the mutation sites in the JM domain (yellow). The structure is shown as a ribbon backbone, with side chains shown as color-coded sticks. Point mutations identified in this study are depicted in red and are annotated. The clustering and location of the point mutations suggest that they reduce the stability of the observed inhibitory conformation of the JM domain. Structural analysis of FLT3-JM-PMs was done with PyMol (DeLano Scientific, San Carlos, CA).