2itp: Difference between revisions
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[[Image:2itp.jpg|left|200px]] | [[Image:2itp.jpg|left|200px]] | ||
'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788''' | {{Structure | ||
|PDB= 2itp |SIZE=350|CAPTION= <scene name='initialview01'>2itp</scene>, resolution 2.74Å | |||
|SITE= <scene name='pdbsite=AC1:Aee+Binding+Site+For+Residue+A+2019'>AC1</scene> | |||
|LIGAND= <scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2ITP is a [ | 2ITP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITP OCA]. | ||
==Reference== | ==Reference== | ||
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity., Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ, Cancer Cell. 2007 Mar;11(3):217-27. PMID:[http:// | Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity., Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ, Cancer Cell. 2007 Mar;11(3):217-27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17349580 17349580] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
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[[Category: egfr]] | [[Category: egfr]] | ||
[[Category: epidermal growth factor]] | [[Category: epidermal growth factor]] | ||
[[Category: | [[Category: g719]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
[[Category: kinase]] | [[Category: kinase]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:33:14 2008'' | ||
Revision as of 18:33, 20 March 2008
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| , resolution 2.74Å | |||||||
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| Sites: | |||||||
| Ligands: | |||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, susceptibility to OMIM:[131550]
About this StructureAbout this Structure
2ITP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity., Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ, Cancer Cell. 2007 Mar;11(3):217-27. PMID:17349580
Page seeded by OCA on Thu Mar 20 17:33:14 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Receptor protein-tyrosine kinase
- Single protein
- Boggon, T J.
- Eck, M J.
- Greulich, H.
- Li, Y.
- Meyerson, M.
- Woo, S.
- Yun, C H.
- AEE
- Aee788
- Alternative splicing
- Anti-oncogene
- Atp-binding
- Cell cycle
- Disease mutation
- Egfr
- Epidermal growth factor
- G719
- Glycoprotein
- Kinase
- Membrane
- Nucleotide-binding
- Phosphorylation
- Polymorphism
- Receptor
- Transferase
- Transmembrane
- Tyrosine-protein kinase