1Y57

Structure of unphosphorylated c-Src in complex with an inhibitor

1Y57 の概要

• エントリーDOI: 10.2210/pdb1y57/pdb
• 関連するPDBエントリー: 1FMK 1KSW 2PTK 2SRC
• 分子名称: Proto-oncogene tyrosine-protein kinase Src, SULFATE ION, 4-[(4-METHYLPIPERAZIN-1-YL)METHYL]-N-{3-[(4-PYRIDIN-3-YLPYRIMIDIN-2-YL)AMINO]PHENYL}BENZAMIDE, ... (4 entities in total)
• 機能のキーワード: kinase structure, sh3, sh2, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane: P12931
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52589.48

構造登録者

Cowan-Jacob, S.W.,Fendrich, G.,Manley, P.W.,Jahnke, W.,Fabbro, D.,Liebetanz, J.,Meyer, T. (登録日: 2004-12-02, 公開日: 2005-06-21, 最終更新日: 2024-03-13)

主引用文献

Cowan-Jacob, S.W.,Fendrich, G.,Manley, P.W.,Jahnke, W.,Fabbro, D.,Liebetanz, J.,Meyer, T.
The Crystal Structure of a c-Src Complex in an Active Conformation Suggests Possible Steps in c-Src Activation
Structure, 13:861-871, 2005

PubMed Abstract: The regulation of the activity of Abl and Src family tyrosine kinases is mediated by intramolecular interactions between the SH3, SH2, and kinase (SH1) domains. We have determined the crystal structure of an unphosphorylated form of c-Src in which the SH2 domain is not bound to the C-terminal tail. This results in an open structure where the kinase domain adopts an active conformation and the C terminus binds within a hydrophobic pocket in the C-terminal lobe. NMR binding studies support the hypothesis that an N-terminal myristate could bind in this pocket, as observed for Abl, suggesting that c-Src may also be regulated by myristate binding. In addition, the structure contains a des-methyl analog of the antileukemia drug imatinib (STI571; Gleevec). This structure reveals why the drug shows a low affinity for active kinase conformations, contributing to its excellent kinase selectivity profile.

PubMed: 15939018
DOI: 10.1016/j.str.2005.03.012

実験手法

X-RAY DIFFRACTION (1.91 Å)