2J6M
Crystal structure of EGFR kinase domain in complex with AEE788
Summary for 2J6M
| Entry DOI | 10.2210/pdb2j6m/pdb |
| Related | 1DNQ 1DNR 1IVO 1M14 1M17 1MOX 1NQL 1XKK 1YY9 1Z9I 2GS2 2GS7 2ITN 2ITO 2ITP 2ITQ 2ITT 2ITU 2ITV 2ITW 2ITX 2ITY 2ITZ 2J5E 2J5F |
| Descriptor | EPIDERMAL GROWTH FACTOR RECEPTOR, 6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE (3 entities in total) |
| Functional Keywords | cell cycle, atp-binding, transferase, polymorphism, nucleotide-binding, alternative splicing, tyrosine-protein kinase, epidermal growth factor, ubl conjugation, phosphorylation, disease mutation, glycoprotein, anti-oncogene, transmembrane, egfr, kinase, aee788, membrane, receptor, wild-type |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533 |
| Total number of polymer chains | 1 |
| Total formula weight | 37744.71 |
| Authors | Yun, C.-H.,Boggon, T.J.,Li, Y.,Woo, S.,Greulich, H.,Meyerson, M.,Eck, M.J. (deposition date: 2006-09-29, release date: 2007-04-03, Last modification date: 2023-12-13) |
| Primary citation | Yun, C.-H.,Boggon, T.J.,Li, Y.,Woo, S.,Greulich, H.,Meyerson, M.,Eck, M.J. Structures of Lung Cancer-Derived Egfr Mutants and Inhibitor Complexes: Mechanism of Activation and Insights Into Differential Inhibitor Sensitivity Cancer Cell, 11:217-, 2007 Cited by PubMed Abstract: 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 with both wild-type and mutant kinases reveal similar binding modes for gefitinib and AEE788, but a marked rotation of the staurosporine in the G719S mutant. Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild-type enzyme. PubMed: 17349580DOI: 10.1016/J.CCR.2006.12.017 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
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