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Figure 3.
Sunitinib recognizes the autoinhibited form of KIT. WT KIT
bound to sunitinib is shown in yellow (JM domain, red; A-loop,
green; C α-helix, cyan). (A) WT KIT bound to sunitinib is very
similar to the published autoinhibited structure of KIT (gray)
(7, 8). Amino acid side chains are shown at the sites of A-loop
substitutions found in sunitinib-resistant GISTs. (B)
Sunitinib-binding site in the complex and apo structures. Drug
binding induces a slight rearrangement of the Phe-811 side chain
relative to the apo form. (C) The overall structure of the D816H
mutant bound to sunitinib (darker blue) is very similar to that
with WT, except for the proposed dislocation of the JM domain
from its autoinhibitory position. Residue 816 is shown for both
proteins.
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