3MS9

ABL kinase in complex with imatinib and a fragment (FRAG1) in the myristate pocket

3MS9 の概要

• エントリーDOI: 10.2210/pdb3ms9/pdb
• 関連するPDBエントリー: 3MSS
• 分子名称: Tyrosine-protein kinase ABL1, 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE, methyl 2-amino-4-chlorobenzoate, ... (5 entities in total)
• 機能のキーワード: kinase, fragment-based screening, fbs, transferase, transferase-transferase regulator complex, transferase/transferase regulator
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm, cytoskeleton: P00520
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69058.19

構造登録者

Cowan-Jacob, S.W.,Rummel, G.,Fendrich, G. (登録日: 2010-04-29, 公開日: 2010-05-26, 最終更新日: 2024-02-21)

主引用文献

Jahnke, W.,Grotzfeld, R.M.,Pelle, X.,Strauss, A.,Fendrich, G.,Cowan-Jacob, S.W.,Cotesta, S.,Fabbro, D.,Furet, P.,Mestan, J.,Marzinzik, A.L.
Binding or bending: distinction of allosteric Abl kinase agonists from antagonists by an NMR-based conformational assay.
J.Am.Chem.Soc., 132:7043-7048, 2010

PubMed Abstract: Allosteric inhibitors of Bcr-Abl have emerged as a novel therapeutic option for the treatment of CML. Using fragment-based screening, a search for novel Abl inhibitors that bind to the myristate pocket was carried out. Here we show that not all myristate ligands are functional inhibitors, but that the conformational state of C-terminal helix_I is a structural determinant for functional activity. We present an NMR-based conformational assay to monitor the conformation of this crucial helix_I and show that myristate ligands that bend helix_I are functional antagonists, whereas ligands that bind to the myristate pocket but do not induce this conformational change are kinase agonists. Activation of c-Abl by allosteric agonists has been confirmed in a biochemical assay.

PubMed: 20450175
DOI: 10.1021/ja101837n

実験手法

X-RAY DIFFRACTION (1.8 Å)