8UF6

Structure of Trek-1(K2P2.1) with ML336

8UF6 の概要

• エントリーDOI: 10.2210/pdb8uf6/pdb
• 関連するPDBエントリー: 8UE2 8UE9 8UEC
• 分子名称: Potassium channel subfamily K member 2, HEXADECANE, N-[(2,4-dichlorophenyl)methyl]-4-propanamidobenzamide, ... (10 entities in total)
• 機能のキーワード: membrane preotein, ml335, trek1, trek-1, malemide, trek-1 ligand, crystal, trans-membrane protein, transmembrane protein, k2p, two pore potassium channel, potassium channel, kcnk2, potassium channel subfamily k member 2, membrane protein, ml336, lh9
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66509.44

構造登録者

Lolicato, M.,Mondal, A.,Minor, D.L. (登録日: 2023-10-03, 公開日: 2024-06-26, 最終更新日: 2025-01-08)

主引用文献

Deal, P.E.,Lee, H.,Mondal, A.,Lolicato, M.,Mendonca, P.R.F.,Black, H.,Jang, S.,El-Hilali, X.,Bryant, C.,Isacoff, E.Y.,Renslo, A.R.,Minor Jr., D.L.
Development of covalent chemogenetic K 2P channel activators.
Cell Chem Biol, 31:1305-1323.e9, 2024

PubMed Abstract: K potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (covalent activation of TREK family K channels to clamp membrane potential) that leverages the discovery of a K modulator pocket site that reacts with electrophile-bearing derivatives of a TREK subfamily small-molecule activator, ML335, to activate the channel irreversibly. We show that CATKLAMP can be used to probe fundamental aspects of K function, as a switch to silence neuronal firing, and is applicable to all TREK subfamily members. Together, our findings exemplify a means to alter K channel activity that should facilitate molecular and systems level studies of K function and enable the search for new K modulators.

PubMed: 39029456
DOI: 10.1016/j.chembiol.2024.06.006

実験手法

X-RAY DIFFRACTION (2.9 Å)