5MJA

Kinase domain of human EphB1 bound to a quinazoline-based inhibitor

5MJA の概要

• エントリーDOI: 10.2210/pdb5mja/pdb
• 分子名称: Ephrin type-B receptor 1, 2-chloranyl-~{N}-[4-[(2-chloranyl-5-oxidanyl-phenyl)amino]quinazolin-7-yl]ethanamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: receptor tyrosine kinase, kinase domain, inhibitor, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P54762
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70633.75

構造登録者

Kung, A.,Schimpl, M.,Chen, Y.-C.,Overman, R.C.,Zhang, C. (登録日: 2016-11-30, 公開日: 2017-05-17, 最終更新日: 2024-11-20)

主引用文献

Kung, A.,Schimpl, M.,Ekanayake, A.,Chen, Y.C.,Overman, R.,Zhang, C.
A Chemical-Genetic Approach to Generate Selective Covalent Inhibitors of Protein Kinases.
ACS Chem. Biol., 12:1499-1503, 2017

PubMed Abstract: Although a previously developed bump-hole approach has proven powerful in generating specific inhibitors for mapping functions of protein kinases, its application is limited by the intolerance of the large-to-small mutation by certain kinases and the inability to control two kinases separately in the same cells. Herein, we describe the development of an alternative chemical-genetic approach to overcome these limitations. Our approach features the use of an engineered cysteine residue at a particular position as a reactive feature to sensitize a kinase of interest to selective covalent blockade by electrophilic inhibitors and is thus termed the Ele-Cys approach. We successfully applied the Ele-Cys approach to identify selective covalent inhibitors of a receptor tyrosine kinase EphB1 and solved cocrystal structures to determine the mode of covalent binding. Importantly, the Ele-Cys and bump-hole approaches afforded orthogonal inhibition of two distinct kinases in the cell, opening the door to their combined use in the study of multikinase signaling pathways.

PubMed: 28459525
DOI: 10.1021/acschembio.6b01083

実験手法

X-RAY DIFFRACTION (2.14 Å)