Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.

@article{Yun2007StructuresOL,
  title={Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.},
  author={Cai-hong Yun and Titus J Boggon and Yiqun Li and Michele S. Woo and H. -G. Greulich and Matthew Meyerson and Michael J. Eck},
  journal={Cancer cell},
  year={2007},
  volume={11 3},
  pages={217-27}
}
Mutations in the EGFR kinase are a cause of non-small-cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788, and a staurosporine. We find that the mutations activate the kinase by disrupting autoinhibitory interactions, and that they accelerate catalysis as much as 50-fold in vitro. Structures of inhibitors in complex… CONTINUE READING
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