4A98

X-ray structure of a pentameric ligand gated ion channel from Erwinia chrysanthemi (ELIC) in complex with bromoflurazepam

4A98 の概要

• エントリーDOI: 10.2210/pdb4a98/pdb
• 関連するPDBエントリー: 2YKS 4A96 4A97
• 分子名称: CYS-LOOP LIGAND-GATED ION CHANNEL, 7-BROMO-1-[2-(DIETHYLAMINO)ETHYL]-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE (2 entities in total)
• 機能のキーワード: transport protein, cys-loop receptor, gaba-a receptor, benzodiazepine
• 由来する生物種: ERWINIA CHRYSANTHEMI
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein (Probable): P0C7B7
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 358156.96

構造登録者

Spurny, R.,Brams, M.,Nury, H.,Legrand, P.,Ulens, C. (登録日: 2011-11-24, 公開日: 2012-10-17, 最終更新日: 2025-10-01)

主引用文献

Spurny, R.,Ramerstorfer, J.,Price, K.,Brams, M.,Ernst, M.,Nury, H.,Verheij, M.,Legrand, P.,Bertrand, D.,Bertrand, S.,Dougherty, D.A.,De Esch, I.J.P.,Corringer, P.,Sieghart, W.,Lummis, S.C.R.,Ulens, C.
Pentameric Ligand-Gated Ion Channel Elic is Activated by Gaba and Modulated by Benzodiazepines.
Proc.Natl.Acad.Sci.USA, 109:E3028-, 2012

PubMed Abstract: GABA(A) receptors are pentameric ligand-gated ion channels involved in fast inhibitory neurotransmission and are allosterically modulated by the anxiolytic, anticonvulsant, and sedative-hypnotic benzodiazepines. Here we show that the prokaryotic homolog ELIC also is activated by GABA and is modulated by benzodiazepines with effects comparable to those at GABA(A) receptors. Crystal structures reveal important features of GABA recognition and indicate that benzodiazepines, depending on their concentration, occupy two possible sites in ELIC. An intrasubunit site is adjacent to the GABA-recognition site but faces the channel vestibule. A second intersubunit site partially overlaps with the GABA site and likely corresponds to a low-affinity benzodiazepine-binding site in GABA(A) receptors that mediates inhibitory effects of the benzodiazepine flurazepam. Our study offers a structural view how GABA and benzodiazepines are recognized at a GABA-activated ion channel.

PubMed: 23035248
DOI: 10.1073/PNAS.1208208109

実験手法

X-RAY DIFFRACTION (3.61 Å)