6XR6

Abl 1b isoform active state

6XR6 の概要

• エントリーDOI: 10.2210/pdb6xr6/pdb
• NMR情報: BMRB: 30770
• 分子名称: Tyrosine-protein kinase ABL1 (1 entity in total)
• 機能のキーワード: abl kinase, oncoprotein
• 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: 33180.90

構造登録者

Xie, T.,Saleh, T.,Rossi, P.,Kalodimos, C.G. (登録日: 2020-07-11, 公開日: 2020-10-07, 最終更新日: 2024-05-15)

主引用文献

Xie, T.,Saleh, T.,Rossi, P.,Kalodimos, C.G.
Conformational states dynamically populated by a kinase determine its function.
Science, 370:-, 2020

PubMed Abstract: Protein kinases intrinsically sample a number of conformational states with distinct catalytic and binding activities. We used nuclear magnetic resonance spectroscopy to describe in atomic-level detail how Abl kinase interconverts between an active and two discrete inactive structures. Extensive differences in key structural elements between the conformational states give rise to multiple intrinsic regulatory mechanisms. The findings explain how oncogenic mutants can counteract inhibitory mechanisms to constitutively activate the kinase. Energetic dissection revealed the contributions of the activation loop, the Asp-Phe-Gly (DFG) motif, the regulatory spine, and the gatekeeper residue to kinase regulation. Characterization of the transient conformation to which the drug imatinib binds enabled the elucidation of drug-resistance mechanisms. Structural insight into inactive states highlights how they can be leveraged for the design of selective inhibitors.

PubMed: 33004676
DOI: 10.1126/science.abc2754

実験手法

SOLUTION NMR