FIGURE 1.

Overall structure of HER2·SYR127063 and EGFR·TAK-285. Comparison of the overall structure of HER2 inhibited by SYR127063 (A) and of EGFR inhibited by TAK-285 (B). For HER2·SYR127063, the kinase domain is represented as a yellow schematic. For EGFR·TAK-285, the kinase domain is represented as a slate blue schematic. For both structures, α-helix C and the A-loop are colored red and tan, respectively. SYR127063 and TAK-285 are shown in a green stick representation colored by atom type. HER2 represents the active-like form of the kinase with the A-loop in an extended conformation. EGFR represents the inactive form of the kinase with a short α-helix present in the N-portion of the A-loop that stabilizes the active-site outward conformation of the α-helix C. αh, α-helix.