Figure 4 - full size

Figure 4. Figure 4. Drug Binding Modes in the Wild-Type and Mutant EGFR Kinase The binding modes of gefitinib (A, C, and E) and AEE788 (B, D, and F) are compared in the wild-type (yellow), L858R (green), and G719S (blue) kinases. Key side chains are labeled, the inhibitors are shown in stick form with carbons colored yellow, and hydrogen bonds are indicated with dashed lines. Compare binding of different inhibitors to the same mutant within rows and binding of the same inhibitor among wild-type and mutants within columns. Binding modes of both compounds are essentially the same in all three structures. Note also the closely corresponding orientations of the pyrrolopyrimidine scaffold in the AEE788 complexes and the quinazoline core in the gefitinib complexes. Additionally, the phenylethyl amine moiety in AEE788 occupies the same space as the aniline substituent in the gefitinib and erlotinib complexes.