5N63

Crystal Structure of p38alpha in Complex with Lipid Pocket Ligand 9c

5N63 の概要

• エントリーDOI: 10.2210/pdb5n63/pdb
• 分子名称: Mitogen-activated protein kinase 14, ~{N}4-[(4-fluorophenyl)methyl]-2-phenyl-quinazoline-4,7-diamine (3 entities in total)
• 機能のキーワード: kinase, small molecule, lipid pocket, p38, quinazoline, transferase
• 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: 41687.58

構造登録者

Buehrmann, M.,Mueller, M.P.,Rauh, D. (登録日: 2017-02-14, 公開日: 2017-09-20, 最終更新日: 2024-01-17)

主引用文献

Buhrmann, M.,Wiedemann, B.M.,Muller, M.P.,Hardick, J.,Ecke, M.,Rauh, D.
Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38 alpha MAPK.
PLoS ONE, 12:e0184627-e0184627, 2017

PubMed Abstract: In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.

PubMed: 28892510
DOI: 10.1371/journal.pone.0184627

実験手法

X-RAY DIFFRACTION (2.4 Å)