4DGG

c-SRC kinase domain in complex with RM-1-176

4DGG の概要

• エントリーDOI: 10.2210/pdb4dgg/pdb
• 関連するPDBエントリー: 3uqf 3uqg
• 分子名称: Proto-oncogene tyrosine-protein kinase Src, 3-{6-[(3-chlorobenzyl)oxy]naphthalen-2-yl}-1-(propan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: tyrosine protein kinase, atp-binding, kinase domain, transferase
• 由来する生物種: Gallus gallus (bantam,chickens)
• 細胞内の位置: Cell membrane (By similarity): P00523
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66341.15

構造登録者

Merritt, E.A.,Larson, E.T. (登録日: 2012-01-25, 公開日: 2012-10-10, 最終更新日: 2024-02-28)

主引用文献

Krishnamurty, R.,Brigham, J.L.,Leonard, S.E.,Ranjitkar, P.,Larson, E.T.,Dale, E.J.,Merritt, E.A.,Maly, D.J.
Active site profiling reveals coupling between domains in SRC-family kinases.
Nat.Chem.Biol., 9:43-50, 2013

PubMed Abstract: Protein kinases, key regulators of intracellular signal transduction, have emerged as an important class of drug targets. Chemical proteomic tools that facilitate the functional interrogation of protein kinase active sites are powerful reagents for studying the regulation of this large enzyme family and performing inhibitor selectivity screens. Here we describe a new crosslinking strategy that enables rapid and quantitative profiling of protein kinase active sites in lysates and live cells. Applying this methodology to the SRC-family kinases (SFKs) SRC and HCK led to the identification of a series of conformation-specific, ATP-competitive inhibitors that have a distinct preference for the autoinhibited forms of these kinases. Furthermore, we show that ligands that have this selectivity are able to modulate the ability of the regulatory domains of SRC and HCK to engage in intermolecular binding interactions. These studies provide insight into the regulation of this important family of tyrosine kinases.

PubMed: 23143416
DOI: 10.1038/nchembio.1118

実験手法

X-RAY DIFFRACTION (2.65 Å)