6TCA

Phosphorylated p38 and MAPKAPK2 complex with inhibitor

6TCA の概要

• エントリーDOI: 10.2210/pdb6tca/pdb
• 分子名称: MAP kinase-activated protein kinase 2, Mitogen-activated protein kinase 14, N-[5-(dimethylsulfamoyl)-2-methylphenyl]-1-phenyl-5-propyl-1H-pyrazole-4-carboxamide (3 entities in total)
• 機能のキーワード: mapk, mapkapk, phosphorylated, p38, mk2, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 340485.94

構造登録者

Sok, P.,Remenyi, A. (登録日: 2019-11-05, 公開日: 2020-07-22, 最終更新日: 2024-10-09)

主引用文献

Sok, P.,Gogl, G.,Kumar, G.S.,Alexa, A.,Singh, N.,Kirsch, K.,Sebo, A.,Drahos, L.,Gaspari, Z.,Peti, W.,Remenyi, A.
MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.
Structure, 28:1101-1113.e5, 2020

PubMed Abstract: Mitogen-activated protein kinases (MAPKs) control essential eukaryotic signaling pathways. While much has been learned about MAPK activation, much less is known about substrate recruitment and specificity. MAPK substrates may be other kinases that are crucial to promote a further diversification of the signaling outcomes. Here, we used a variety of molecular and cellular tools to investigate the recruitment of two substrate kinases, RSK1 and MK2, to three MAPKs (ERK2, p38α, and ERK5). Unexpectedly, we identified that kinase heterodimers form structurally and functionally distinct complexes depending on the activation state of the MAPK. These may be incompatible with downstream signaling, but naturally they may also form structures that are compatible with the phosphorylation of the downstream kinase at the activation loop, or alternatively at other allosteric sites. Furthermore, we show that small-molecule inhibitors may affect the quaternary arrangement of kinase heterodimers and thus influence downstream signaling in a specific manner.

PubMed: 32649858
DOI: 10.1016/j.str.2020.06.007

実験手法

X-RAY DIFFRACTION (3.7 Å)