3T9V

CNQX bound to a reduced double cysteine mutant (A452C/S652C) of the ligand binding domain of GluA2

3T9V の概要

• エントリーDOI: 10.2210/pdb3t9v/pdb
• 関連するPDBエントリー: 3T93 3T96 3T9H 3T9U 3T9X
• 分子名称: Glutamate receptor 2, 7-nitro-2,3-dioxo-2,3-dihydroquinoxaline-6-carbonitrile, ZINC ION, ... (4 entities in total)
• 機能のキーワード: s1s2, neurotransmitter receptor, transport protein
• 由来する生物種: Rattus norvegicus (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: 58488.82

構造登録者

Ahmed, A.H.,Oswald, R.E. (登録日: 2011-08-03, 公開日: 2011-08-17, 最終更新日: 2023-09-13)

主引用文献

Ahmed, A.H.,Wang, S.,Chuang, H.H.,Oswald, R.E.
Mechanism of AMPA Receptor Activation by Partial Agonists: DISULFIDE TRAPPING OF CLOSED LOBE CONFORMATIONS.
J.Biol.Chem., 286:35257-35266, 2011

PubMed Abstract: The mechanism by which agonist binding to an ionotropic glutamate receptor leads to channel opening is a central issue in molecular neurobiology. Partial agonists are useful tools for studying the activation mechanism because they produce full channel activation with lower probability than full agonists. Structural transitions that determine the efficacy of partial agonists can provide information on the trigger that begins the channel-opening process. The ligand-binding domain of AMPA receptors is a bilobed structure, and the closure of the lobes is associated with channel activation. One possibility is that partial agonists sterically block full lobe closure but that partial degrees of closure trigger the channel with a lower probability. Alternatively, full lobe closure may be required for activation, and the stability of the fully closed state could determine efficacy with the fully closed state having a lower stability when bound to partial relative to full agonists. Disulfide-trapping experiments demonstrated that even extremely low efficacy ligands such as 6-cyano-7-nitroquinoxaline-2,3-dione can produce a full lobe closure, presumably with low probability. The results are consistent the hypothesis that the efficacy is determined at least in part by the stability of the state in which the lobes are fully closed.

PubMed: 21846932
DOI: 10.1074/jbc.M111.269001

実験手法

X-RAY DIFFRACTION (1.975 Å)