2FO0

Organization of the SH3-SH2 Unit in Active and Inactive Forms of the c-Abl Tyrosine Kinase

2FO0 の概要

• エントリーDOI: 10.2210/pdb2fo0/pdb
• 分子名称: Proto-oncogene tyrosine-protein kinase ABL1 (1B ISOFORM), MYRISTIC ACID, 6-(2,6-DICHLOROPHENYL)-2-{[3-(HYDROXYMETHYL)PHENYL]AMINO}-8-METHYLPYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE, ... (5 entities in total)
• 機能のキーワード: n-terminal cap, autoinhibition, myristoylation, sh3-sh2 clamp, phosphoserine, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57292.21

構造登録者

Nagar, B.,Hantschel, O.,Seeliger, M.,Davies, J.M.,Weis, W.I.,Superti-Furga, G.,Kuriyan, J. (登録日: 2006-01-12, 公開日: 2006-03-21, 最終更新日: 2024-10-30)

主引用文献

Nagar, B.,Hantschel, O.,Seeliger, M.,Davies, J.M.,Weis, W.I.,Superti-Furga, G.,Kuriyan, J.
Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase.
Mol.Cell, 21:787-798, 2006

PubMed Abstract: The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 and SH2 domains with the distal surface of the kinase domain. We present a crystal structure of a fragment of c-Abl which reveals that a critical N-terminal cap segment, not visualized in previous structures, buttresses the SH3-SH2 substructure in the autoinhibited state and locks it onto the distal surface of the kinase domain. Surprisingly, the N-terminal cap is phosphorylated on a serine residue that interacts with the connector between the SH3 and SH2 domains. Small-angle X-ray scattering (SAXS) analysis shows that a mutated form of c-Abl, in which the N-terminal cap and two other key contacts in the autoinhibited state are deleted, exists in an extended array of the SH3, SH2, and kinase domains. This alternative conformation of Abl is likely to prolong the active state of the kinase by preventing it from returning to the autoinhibited state.

PubMed: 16543148
DOI: 10.1016/j.molcel.2006.01.035

実験手法

X-RAY DIFFRACTION (2.27 Å)