6HJI

Xray structure of GLIC in complex with crotonate

6HJI の概要

• エントリーDOI: 10.2210/pdb6hji/pdb
• 分子名称: Proton-gated ion channel, DIUNDECYL PHOSPHATIDYL CHOLINE, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: pentameric ligand-gated ion channel, membrane 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: 194788.64

構造登録者

Fourati, Z.,Delarue, M. (登録日: 2018-09-03, 公開日: 2019-09-18, 最終更新日: 2024-05-15)

主引用文献

Fourati, Z.,Sauguet, L.,Delarue, M.
Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel.
Acta Crystallogr D Struct Biol, 76:668-675, 2020

PubMed Abstract: GLIC is a bacterial homologue of the pentameric ligand-gated ion channels (pLGICs) that mediate the fast chemical neurotransmission of nerve signalling in eukaryotes. Because the activation and allosteric modulation features are conserved among prokaryotic and eukaryotic pLGICs, GLIC is commonly used as a model to study the allosteric transition and structural pharmacology of pLGICs. It has previously been shown that GLIC is inhibited by some carboxylic acid derivatives. Here, experimental evidence for carboxylate binding to GLIC is provided by solving its X-ray structures with a series of monocarboxylate and dicarboxylate derivatives, and two carboxylate-binding sites are described: (i) the `intersubunit' site that partially overlaps the canonical pLGIC orthosteric site and (ii) the `intrasubunit' vestibular site, which is only occupied by a subset of the described derivatives. While the intersubunit site is widely conserved in all pLGICs, the intrasubunit site is only conserved in cationic eukaryotic pLGICs. This study sheds light on the importance of these two extracellular modulation sites as potential drug targets in pLGICs.

PubMed: 32627739
DOI: 10.1107/S205979832000772X

実験手法

X-RAY DIFFRACTION (2.8 Å)