Figure 3. Structural analysis of the EGFR kinase domain mutations. The EGFR kinase domain crystal structure (PDB accession code 2GS6) is shown in complex with an ATP analogue-peptide conjugate. Two kinase domains are depicted here to illustrate the Cdk/cyclin-like activating asymmetrical dimerization interface elegantly proposed by Zhang et al. (24). The two EGFR kinase domain molecules are shown in cartoon format and colored blue and brown with their activation loops colored orange. The kinase domain mutations identified in this study are indicated with space-filling spheres and are colored with oxygen atoms in red and nitrogen atoms in blue. The locations of activating mutation L858R and the resistance mutation T790M are indicated with red spheres. The ATP analogue-peptide conjugate solved in this crystal structure is indicated with the ATP moiety shown in stick format and colored according to atom type. The top exploded view shows the location of residues E931 and K929 in the intermolecular interface packed against the surface (in gray) of the partner kinase domain. The bottom exploded view shows the location of the mutations found in the vicinity of the ATP-binding pocket. The figure was prepared using the program PYMOL (http://www.pymol.org).