1m14: Difference between revisions
New page: left|200px<br /> <applet load="1m14" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m14, resolution 2.60Å" /> '''Tyrosine Kinase Dom... |
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[[Image:1m14.gif|left|200px]]<br /> | [[Image:1m14.gif|left|200px]]<br /><applet load="1m14" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1m14, resolution 2.60Å" /> | caption="1m14, resolution 2.60Å" /> | ||
'''Tyrosine Kinase Domain from Epidermal Growth Factor Receptor'''<br /> | '''Tyrosine Kinase Domain from Epidermal Growth Factor Receptor'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structure of the kinase domain from the epidermal growth | The crystal structure of the kinase domain from the epidermal growth factor receptor (EGFRK) including forty amino acids from the carboxyl-terminal tail has been determined to 2.6-A resolution, both with and without an EGFRK-specific inhibitor currently in Phase III clinical trials as an anti-cancer agent, erlotinib (OSI-774, CP-358,774, Tarceva(TM)). The EGFR family members are distinguished from all other known receptor tyrosine kinases in possessing constitutive kinase activity without a phosphorylation event within their kinase domains. Despite its lack of phosphorylation, we find that the EGFRK activation loop adopts a conformation similar to that of the phosphorylated active form of the kinase domain from the insulin receptor. Surprisingly, key residues of a putative dimerization motif lying between the EGFRK domain and carboxyl-terminal substrate docking sites are found in close contact with the kinase domain. Significant intermolecular contacts involving the carboxyl-terminal tail are discussed with respect to receptor oligomerization. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1M14 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | 1M14 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M14 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Eigenbrot, C.]] | [[Category: Eigenbrot, C.]] | ||
[[Category: Sliwkowski, M | [[Category: Sliwkowski, M X.]] | ||
[[Category: Stamos, J.]] | [[Category: Stamos, J.]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
[[Category: tyrosine kinase domain]] | [[Category: tyrosine kinase domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:50:23 2008'' | ||
Revision as of 14:50, 21 February 2008
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Tyrosine Kinase Domain from Epidermal Growth Factor Receptor
OverviewOverview
The crystal structure of the kinase domain from the epidermal growth factor receptor (EGFRK) including forty amino acids from the carboxyl-terminal tail has been determined to 2.6-A resolution, both with and without an EGFRK-specific inhibitor currently in Phase III clinical trials as an anti-cancer agent, erlotinib (OSI-774, CP-358,774, Tarceva(TM)). The EGFR family members are distinguished from all other known receptor tyrosine kinases in possessing constitutive kinase activity without a phosphorylation event within their kinase domains. Despite its lack of phosphorylation, we find that the EGFRK activation loop adopts a conformation similar to that of the phosphorylated active form of the kinase domain from the insulin receptor. Surprisingly, key residues of a putative dimerization motif lying between the EGFRK domain and carboxyl-terminal substrate docking sites are found in close contact with the kinase domain. Significant intermolecular contacts involving the carboxyl-terminal tail are discussed with respect to receptor oligomerization.
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
1M14 is a Single protein structure of sequence from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
ReferenceReference
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor., Stamos J, Sliwkowski MX, Eigenbrot C, J Biol Chem. 2002 Nov 29;277(48):46265-72. Epub 2002 Aug 23. PMID:12196540
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