3BCE

Crystal structure of the ErbB4 kinase

3BCE の概要

• エントリーDOI: 10.2210/pdb3bce/pdb
• 関連するPDBエントリー: 3BBT 3BBW
• 分子名称: Receptor tyrosine-protein kinase erbB-4, MANGANESE (II) ION, TETRAETHYLENE GLYCOL, ... (5 entities in total)
• 機能のキーワード: active conformation, atp-binding, glycoprotein, kinase, membrane, nucleotide-binding, phosphorylation, receptor, transferase, transmembrane, tyrosine-protein kinase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein . ERBB4 intracellular domain: Nucleus : Q15303
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 112829.65

構造登録者

Qiu, C. (登録日: 2007-11-12, 公開日: 2008-02-12, 最終更新日: 2024-02-21)

主引用文献

Qiu, C.,Tarrant, M.K.,Choi, S.H.,Sathyamurthy, A.,Bose, R.,Banjade, S.,Pal, A.,Bornmann, W.G.,Lemmon, M.A.,Cole, P.A.,Leahy, D.J.
Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase.
Structure, 16:460-467, 2008

PubMed Abstract: HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members.

PubMed: 18334220
DOI: 10.1016/j.str.2007.12.016

実験手法

X-RAY DIFFRACTION (2.5 Å)