5FHM

Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with (S)-2-Amino-3-(5-(2-(3-(aminomethyl)benzyl)-2H-tetrazol-5-yl)-3-hydroxyisoxazol-4-yl)propanoic acid at resolution 1.55 A resolution

5FHM の概要

• エントリーDOI: 10.2210/pdb5fhm/pdb
• 関連するPDBエントリー: 2P2A
• 分子名称: Glutamate receptor 2,Glutamate receptor 2, SULFATE ION, (2~{S})-3-[5-[2-[[3-(aminomethyl)phenyl]methyl]-1,2,3,4-tetrazol-5-yl]-3-oxidanyl-1,2-oxazol-4-yl]-2-azanyl-propanoic acid, ... (8 entities in total)
• 機能のキーワード: ionotropic glutamate receptor glua2, ligand-binding domain, membrane protein
• 由来する生物種: Rattus norvegicus (Norway Rat); 詳細
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : P19491
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60361.90

構造登録者

Kastrup, J.S.,Frydenvang, K.,Al-musaed, A. (登録日: 2015-12-22, 公開日: 2016-03-02, 最終更新日: 2024-11-06)

主引用文献

Wang, S.Y.,Larsen, Y.,Navarrete, C.V.,Jensen, A.A.,Nielsen, B.,Al-Musaed, A.,Frydenvang, K.,Kastrup, J.S.,Pickering, D.S.,Clausen, R.P.
Tweaking Subtype Selectivity and Agonist Efficacy at (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) Receptors in a Small Series of BnTetAMPA Analogues.
J.Med.Chem., 59:2244-2254, 2016

PubMed Abstract: A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at the four homomeric AMPA receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit very different pharmacological profiles with binding affinity preference for the subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2 show that they induce full domain closure despite their low agonist efficacies. Trp767 in GluA2 ABD could be an important determinant for partial agonism of this compound series at AMPA receptors, since agonist efficacy also correlated with the location of the Trp767 side chain.

PubMed: 26862980
DOI: 10.1021/acs.jmedchem.5b01982

実験手法

X-RAY DIFFRACTION (1.55 Å)