4Z91

ELIC cocrystallized with isofluorane in a desensitized state

4Z91 の概要

• エントリーDOI: 10.2210/pdb4z91/pdb
• 関連するPDBエントリー: 3RQU 3RQW
• 分子名称: Gamma-aminobutyric-acid receptor subunit beta-1, (2R)-2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: elic, isoflurane, anesthetics, desensitized state, transport protein
• 由来する生物種: Dickeya dadantii (strain 3937)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 374240.46

構造登録者

Chen, Q.,Kinde, M.N.,Arjunan, P.,Cohen, A.,Xu, Y.,Tang, P. (登録日: 2015-04-09, 公開日: 2015-09-16, 最終更新日: 2023-09-27)

主引用文献

Chen, Q.,Kinde, M.N.,Arjunan, P.,Wells, M.M.,Cohen, A.E.,Xu, Y.,Tang, P.
Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.
Sci Rep, 5:13833-13833, 2015

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.

PubMed: 26346220
DOI: 10.1038/srep13833

実験手法

X-RAY DIFFRACTION (3.3915 Å)