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J. Biol. Chem., Vol. 277, Issue 48, 46265-46272, November 29, 2002
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From the Departments of 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-Å
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, TarcevaTM). 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.
The atomic coordinates and the structure factors (code 1M14 and 1M17) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Structure of the Epidermal Growth Factor Receptor Kinase Domain
Alone and in Complex with a 4-Anilinoquinazoline Inhibitor*
,¶
Protein Engineering and
§ Molecular Oncology, Genentech, Inc., South San
Francisco, California 94080
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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|
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|
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|
|
|
|
|
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|
|
|
|
|
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|
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|
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|
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|
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|
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