6AMW

Abl1b Regulatory Module 'Activating' conformation

6AMW の概要

• エントリーDOI: 10.2210/pdb6amw/pdb
• 関連するPDBエントリー: 6AMV
• NMR情報: BMRB: 30332
• 分子名称: Tyrosine-protein kinase ABL1 (1 entity in total)
• 機能のキーワード: signaling protein kinase, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28350.39

構造登録者

Kalodimos, C.G.,Rossi, P.,Saleh, T. (登録日: 2017-08-11, 公開日: 2017-09-27, 最終更新日: 2024-05-15)

主引用文献

Saleh, T.,Rossi, P.,Kalodimos, C.G.
Atomic view of the energy landscape in the allosteric regulation of Abl kinase.
Nat. Struct. Mol. Biol., 24:893-901, 2017

PubMed Abstract: The activity of protein kinases is often regulated in an intramolecular fashion by signaling domains, which feature several phosphorylation or protein-docking sites. How kinases integrate such distinct binding and signaling events to regulate their activities is unclear, especially in quantitative terms. We used NMR spectroscopy to show how structural elements within the Abl regulatory module (RM) synergistically generate a multilayered allosteric mechanism that enables Abl kinase to function as a finely tuned switch. We dissected the structure and energetics of the regulatory mechanism to precisely measure the effects of various activating or inhibiting stimuli on Abl kinase activity. The data provide a mechanistic basis explaining genetic observations and reveal a previously unknown activator region within Abl. Our findings show that drug-resistance mutations in the Abl RM exert their allosteric effect by promoting the activated state of Abl and not by decreasing the drug affinity for the kinase.

PubMed: 28945248
DOI: 10.1038/nsmb.3470

実験手法

SOLUTION NMR