4F8H

X-ray Structure of the Anesthetic Ketamine Bound to the GLIC Pentameric Ligand-gated Ion Channel

4F8H の概要

• エントリーDOI: 10.2210/pdb4f8h/pdb
• 分子名称: Proton-gated ion channel, (R)-ketamine, tetradecyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, ... (5 entities in total)
• 機能のキーワード: ketamine, pentameric ligand-gated ion channel, ion channel, anesthetics, transport protein
• 由来する生物種: Gloeobacter violaceus
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 193710.70

構造登録者

Pan, J.J.,Chen, Q.,Willenbring, D.,Kong, X.P.,Cohen, A.,Xu, Y.,Tang, P. (登録日: 2012-05-17, 公開日: 2012-08-29, 最終更新日: 2023-09-13)

主引用文献

Pan, J.,Chen, Q.,Willenbring, D.,Mowrey, D.,Kong, X.P.,Cohen, A.,Divito, C.B.,Xu, Y.,Tang, P.
Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine.
Structure, 20:1463-1469, 2012

PubMed Abstract: Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but a structural understanding of anesthetic action on pLGICs remains elusive. GLIC, a prokaryotic pLGIC, can be inhibited by anesthetics, including ketamine. The ketamine concentration leading to half-maximal inhibition of GLIC (58 μM) is comparable to that on neuronal nicotinic acetylcholine receptors. A 2.99 Å resolution X-ray structure of GLIC bound with ketamine revealed ketamine binding to an intersubunit cavity that partially overlaps with the homologous antagonist-binding site in pLGICs. The functional relevance of the identified ketamine site was highlighted by profound changes in GLIC activation upon cysteine substitution of the cavity-lining residue N152. The relevance is also evidenced by changes in ketamine inhibition upon the subsequent chemical labeling of N152C. The results provide structural insight into the molecular recognition of ketamine and are valuable for understanding the actions of anesthetics and other allosteric modulators on pLGICs.

PubMed: 22958642
DOI: 10.1016/j.str.2012.08.009

実験手法

X-RAY DIFFRACTION (2.99 Å)