2itx: Difference between revisions
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'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AMP-PNP''' | '''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AMP-PNP''' | ||
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[[Category: Woo, S.]] | [[Category: Woo, S.]] | ||
[[Category: Yun, C H.]] | [[Category: Yun, C H.]] | ||
[[Category: | [[Category: Alternative splicing]] | ||
[[Category: | [[Category: Amp-pnp]] | ||
[[Category: | [[Category: Anp]] | ||
[[Category: | [[Category: Anti-oncogene]] | ||
[[Category: | [[Category: Atp-binding]] | ||
[[Category: | [[Category: Cell cycle]] | ||
[[Category: | [[Category: Disease mutation]] | ||
[[Category: | [[Category: Egfr]] | ||
[[Category: | [[Category: Epidermal growth factor]] | ||
[[Category: | [[Category: Glycoprotein]] | ||
[[Category: | [[Category: Kinase]] | ||
[[Category: | [[Category: Membrane]] | ||
[[Category: | [[Category: Nucleotide-binding]] | ||
[[Category: | [[Category: Phosphorylation]] | ||
[[Category: | [[Category: Polymorphism]] | ||
[[Category: | [[Category: Receptor]] | ||
[[Category: | [[Category: Transferase]] | ||
[[Category: | [[Category: Transmembrane]] | ||
[[Category: | [[Category: Tyrosine-protein kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:52:05 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 07:52, 4 May 2008
CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AMP-PNP
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.
About this StructureAbout this Structure
2ITX 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 Sun May 4 07:52:05 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.
- Alternative splicing
- Amp-pnp
- Anp
- Anti-oncogene
- Atp-binding
- Cell cycle
- Disease mutation
- Egfr
- Epidermal growth factor
- Glycoprotein
- Kinase
- Membrane
- Nucleotide-binding
- Phosphorylation
- Polymorphism
- Receptor
- Transferase
- Transmembrane
- Tyrosine-protein kinase