1OPL

Structural basis for the auto-inhibition of c-Abl tyrosine kinase

1OPL の概要

• エントリーDOI: 10.2210/pdb1opl/pdb
• 関連するPDBエントリー: 1OPJ 1OPK
• 分子名称: proto-oncogene tyrosine-protein kinase, MYRISTIC ACID, 6-(2,6-DICHLOROPHENYL)-2-{[3-(HYDROXYMETHYL)PHENYL]AMINO}-8-METHYLPYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytoskeleton. Isoform IB: Nucleus membrane; Lipid-anchor: P00519
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123122.28

構造登録者

Nagar, B.,Hantschel, O.,Young, M.A.,Scheffzek, K.,Veach, D.,Bornmann, W.,Clarkson, B.,Superti-Furga, G.,Kuriyan, J. (登録日: 2003-03-06, 公開日: 2003-04-08, 最終更新日: 2023-08-16)

主引用文献

Nagar, B.,Hantschel, O.,Young, M.A.,Scheffzek, K.,Veach, D.,Bornmann, W.,Clarkson, B.,Superti-Furga, G.,Kuriyan, J.
Structural basis for the autoinhibition of c-Abl tyrosine kinase
Cell(Cambridge,Mass.), 112:859-871, 2003

PubMed Abstract: c-Abl is normally regulated by an autoinhibitory mechanism, the disruption of which leads to chronic myelogenous leukemia. The details of this mechanism have been elusive because c-Abl lacks a phosphotyrosine residue that triggers the assembly of the autoinhibited form of the closely related Src kinases by internally engaging the SH2 domain. Crystal structures of c-Abl show that the N-terminal myristoyl modification of c-Abl 1b binds to the kinase domain and induces conformational changes that allow the SH2 and SH3 domains to dock onto it. Autoinhibited c-Abl forms an assembly that is strikingly similar to that of inactive Src kinases but with specific differences that explain the differential ability of the drug STI-571/Gleevec/imatinib (STI-571) to inhibit the catalytic activity of Abl, but not that of c-Src.

PubMed: 12654251
DOI: 10.1016/S0092-8674(03)00194-6

実験手法

X-RAY DIFFRACTION (3.42 Å)