1M14

Tyrosine Kinase Domain from Epidermal Growth Factor Receptor

1M14 の概要

• エントリーDOI: 10.2210/pdb1m14/pdb
• 関連するPDBエントリー: 1M17
• 分子名称: Epidermal growth factor receptor (2 entities in total)
• 機能のキーワード: transferase, tyrosine kinase domain
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37875.75

構造登録者

Stamos, J.,Sliwkowski, M.X.,Eigenbrot, C. (登録日: 2002-06-17, 公開日: 2002-09-04, 最終更新日: 2024-02-14)

主引用文献

Stamos, J.,Sliwkowski, M.X.,Eigenbrot, C.
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
J.Biol.Chem., 277:46265-46272, 2002

PubMed Abstract: 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.

PubMed: 12196540
DOI: 10.1074/jbc.M207135200

実験手法

X-RAY DIFFRACTION (2.6 Å)