Figure 2

Molecular characterization of the described insertion in Exon 19 of the EGFR-gene. A) Sanger sequence of the mutation in exon 19 of the EGFR-gene. Indicated by the red frame are the duplicated 18 nucleotides which do not result in a mutation-typical double curve pattern. As wildtype and mutated DNA strands differ beginning with the end of the insertion/duplication, typical double curve pattern is occurring right behind the mutation. B) Molecular model of the mutated protein highlighting the insertion (orange area). Lysin 751 (K751, red) is displaced away from the aromatic ring of gefitinib, thus opening the ATP-binding pocket and changing its electrostatic properties. The 6 aminoacids following the insertion (yellow area) are now in a coiled-coil tertiary structure. C) Molecular model of wildtype EGFR in complex with gefitinib. Lysin 751 (K751, red) is in the vicinity of the aromatic ring of gefitinib. The yellow area is highlighting the site of the duplication.