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Figure 3.
Figure 3: Crystal structure of WZ4002 bound to EGFR T790M. a,
Chemical structures of WZ8040 and WZ4002 are shown schematically
in a manner resembling the conformation adopted in complex with
the kinase. b, Crystal structure of WZ4002 in complex with EGFR
T790M mutant (PDB ID 3IKA). WZ4002 binds the active conformation
of the kinase, with both the regulatory C-helix and the
‘DFG’ segment of the activation loop in their inward, active
positions. The EGFR kinase is shown in a ribbon representation
(blue) with the bound inhibitor in yellow. Side-chain and
main-chain atoms are shown for selected residues that contact
the compound. Expected hydrogen bonds to the backbone amide and
carbonyl atoms of Met 793 are indicated by dashed lines. Note
also the covalent bond with Cys 797. The structure was refined
to a crystallographic R value of 21.3% (R[free] = 25.4%) with
data extending to 2.9-Å resolution (see Methods for
further crystallographic details).
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