EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into binding of therapeutic channel blockers in NMDA receptors.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 29, Issue 6, Page 507-518, Year 2022
掲載日	2022年5月30日
著者	Tsung-Han Chou / Max Epstein / Kevin Michalski / Eve Fine / Philip C Biggin / Hiro Furukawa /
PubMed 要旨	Excitatory signaling mediated by N-methyl-D-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs ...Excitatory signaling mediated by N-methyl-D-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs are of medical interest owing to their potential for treating depression, Alzheimer's disease, and epilepsy. However, precise mechanisms underlying binding and channel blockade have remained limited owing to challenges in obtaining high-resolution structures at the binding site within the transmembrane domains. Here, we monitor the binding of three clinically important channel blockers: phencyclidine, ketamine, and memantine in GluN1-2B NMDARs at local resolutions of 2.5-3.5 Å around the binding site using single-particle electron cryo-microscopy, molecular dynamics simulations, and electrophysiology. The channel blockers form different extents of interactions with the pore-lining residues, which control mostly off-speeds but not on-speeds. Our comparative analyses of the three unique NMDAR channel blockers provide a blueprint for developing therapeutic compounds with minimal side effects.
リンク	Nat Struct Mol Biol / PubMed:35637422 / PubMed Central
手法	EM (単粒子)
解像度	2.97 - 4.3 Å
構造データ	24946 7saa EMDB-24946, PDB-7saa: Glycine and glutamate bound GluN1a-GluN2B NMDA receptors in non-active 1 conformation at 2.97 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.97 Å 24947 7sab EMDB-24947, PDB-7sab: Phencyclidine-bound GluN1a-GluN2B NMDA receptors 手法: EM (単粒子) / 解像度: 4.3 Å 24948 7sac EMDB-24948, PDB-7sac: S-(+)-ketamine bound GluN1a-GluN2B NMDA receptors at 3.69 Angstrom resolution 手法: EM (単粒子) / 解像度: 3.69 Å 24949 7sad EMDB-24949, PDB-7sad: Memantine-bound GluN1a-GluN2B NMDA receptors 手法: EM (単粒子) / 解像度: 3.96 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-GLY: GLYCINE / グリシン / グリシン ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 / グルタミン酸 ChemComp-1PC: 1-(PHENYL-1-CYCLOHEXYL)PIPERIDINE / フェンシクリジン / フェンサイクリジン ChemComp-JC9: (2~{S})-2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one / (S)-ケタミン / 抗うつ薬YM / エスケタミン ChemComp-377: Memantine / メマンチン / 薬剤YM / メマンチン
由来	rattus norvegicus (ドブネズミ)
キーワード	TRANSPORT PROTEIN (運搬体タンパク質) / Ligand-gated ion channel (リガンド依存性イオンチャネル) / ionotropic glutamate receptor / synaptic protein / voltage-gate ion channel / voltage-gated ion channel (電位依存性イオンチャネル)