5O8V

Covalent Inhibitor 4a bound to the Lipid Pocket of p38alpha Mutant S251C

5O8V の概要

• エントリーDOI: 10.2210/pdb5o8v/pdb
• 分子名称: Mitogen-activated protein kinase 14, ~{N}-[3-[7-azanyl-4-(2-phenylethylamino)quinazolin-2-yl]phenyl]propanamide (3 entities in total)
• 機能のキーワード: kinase, small molecule, lipid pocket, p38, covalent, mutant, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41770.76

構造登録者

Buehrmann, M.,Rauh, D. (登録日: 2017-06-14, 公開日: 2017-09-06, 最終更新日: 2024-10-23)

主引用文献

Buhrmann, M.,Hardick, J.,Weisner, J.,Quambusch, L.,Rauh, D.
Covalent Lipid Pocket Ligands Targeting p38 alpha MAPK Mutants.
Angew. Chem. Int. Ed. Engl., 56:13232-13236, 2017

PubMed Abstract: A chemical genetic approach is presented to covalently target a unique lipid binding pocket in the protein kinase p38α, whose function is not yet known. Based on a series of cocrystal structures, a library of 2-arylquinazolines that were decorated with electrophiles were designed and synthesized to covalently target tailored p38α mutants containing artificially introduced cysteine residues. Matching protein-ligand pairs were identified by MS analysis and further validated by MS/MS studies and protein crystallography. The covalent ligands that emerged from this approach showed excellent selectivity towards a single p38α mutant and will be applicable as suitable probes in future studies of biological systems to dissect the function of the lipid pocket by means of pharmacological perturbations.

PubMed: 28834017
DOI: 10.1002/anie.201706345

実験手法

X-RAY DIFFRACTION (2 Å)