Figure 5.
The G719S mutation alters the binding mode of staurosporine analog AFN941. (A) The wild-type EGFR in complex with AFN941. Hydrogen bonds (dashed lines) are formed with the backbone amides of Met 793 in the hinge region and Gly 719 in the P-loop. (B) Structure of the G719S mutant in complex with AFN941. The serine substitution displaces and rotates the inhibitor, disrupting the hydrogen bond with the P-loop and promoting additional interactions with the backbone carbonyls of Gln 791 and Arg 841.