1m17
From Proteopedia
Epidermal Growth Factor Receptor tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib
Overview
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.
About this Structure
1M17 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 00:30:30 2008
