6ODL

Crystal structure of GluN2A agonist binding domain with 4-butyl-(S)-CCG-IV

6ODL の概要

• エントリーDOI: 10.2210/pdb6odl/pdb
• 分子名称: Glutamate receptor ionotropic, NMDA 2A,Glutamate receptor ionotropic, NMDA 2A, (1S,2R)-2-[(S)-amino(carboxy)methyl]-1-butylcyclopropane-1-carboxylic acid (3 entities in total)
• 機能のキーワード: nmda receptor, antagonist, transport protein, receptor
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63138.37

構造登録者

Mou, T.C.,Clausen, R.P.,Sprang, S.R.,Hansen, K.B. (登録日: 2019-03-26, 公開日: 2020-04-01, 最終更新日: 2024-10-30)

主引用文献

Maolanon, A.,Papangelis, A.,Kawiecki, D.,Mou, T.C.,Syrenne, J.T.,Yi, F.,Hansen, K.B.,Clausen, R.P.
Stereoselective synthesis of novel 2'-(S)-CCG-IV analogues as potent NMDA receptor agonists.
Eur.J.Med.Chem., 212:113099-113099, 2021

PubMed Abstract: We developed a versatile stereoselective route for the synthesis of new 2'-(S)-CCG-IV analogues. The route allows for late stage diversification and thereby provides access to a great variety of conformationally restricted cyclopropyl glutamate analogues. A selection of the 2'-(S)-CCG-IV analogues were evaluated using two-electrode voltage-clamp electrophysiology at recombinant GluN1/GluN2A-D receptors, demonstrating that agonists can be developed with GluN2 subunit-dependent potency and agonist efficacy. We also describe a crystal structure of the GluN2A agonist binding domain in complex with 2'-butyl-(S)-CCG-IV that determines the position of 2'-substituents in (S)-CCG-IV agonists in the glutamate binding site and provides further insight to the structural determinants of their agonist efficacy. The stereoselective synthesis described here enables versatile and straight-forward modifications to diverse analogues of interest for the development of potent subtype-specific NMDA receptor agonists and other applications.

PubMed: 33383257
DOI: 10.1016/j.ejmech.2020.113099

実験手法

X-RAY DIFFRACTION (2.3 Å)