登録情報 データベース : EMDB / ID : EMD-24947 ダウンロードとリンクタイトル Phencyclidine-bound GluN1a-GluN2B NMDA receptors マップデータB-factor sharpened map 詳細 試料複合体 : Hetero-tetrameric GluN1a-GluN2B NMDAR receptorsタンパク質・ペプチド : Glutamate receptor ionotropic, NMDA 1タンパク質・ペプチド : Glutamate receptor ionotropic, NMDA 2Bリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : 1-(PHENYL-1-CYCLOHEXYL)PIPERIDINE 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication ... neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / NMDA selective glutamate receptor signaling pathway / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / 感作 / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / EPHB-mediated forward signaling / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / protein localization to postsynaptic membrane / apical dendrite / 樹状突起 / regulation of respiratory gaseous exchange / propylene metabolic process / response to glycine / response to other organism / fear response / response to methylmercury / voltage-gated monoatomic cation channel activity / positive regulation of cysteine-type endopeptidase activity / response to morphine / glutamate-gated calcium ion channel activity / cellular response to dsRNA / response to carbohydrate / regulation of monoatomic cation transmembrane transport / interleukin-1 receptor binding / negative regulation of dendritic spine maintenance / cellular response to lipid / positive regulation of glutamate secretion / NMDA glutamate receptor activity / response to growth hormone / NMDA selective glutamate receptor complex / RAF/MAP kinase cascade / Synaptic adhesion-like molecules / parallel fiber to Purkinje cell synapse / calcium ion transmembrane import into cytosol / response to manganese ion / protein heterotetramerization / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / neuromuscular process / regulation of synapse assembly / 活動電位 / glycine binding / positive regulation of calcium ion transport into cytosol / male mating behavior / regulation of neuronal synaptic plasticity / regulation of dendrite morphogenesis / regulation of axonogenesis / heterocyclic compound binding / receptor clustering / suckling behavior / behavioral response to pain / startle response / response to amine / monoatomic cation transmembrane transport / social behavior / small molecule binding / regulation of MAPK cascade / positive regulation of excitatory postsynaptic potential / ligand-gated monoatomic ion channel activity / response to magnesium ion / 学習 / monoatomic cation transport / excitatory synapse / positive regulation of dendritic spine maintenance / extracellularly glutamate-gated ion channel activity / cellular response to organic cyclic compound / neuron development / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / glutamate receptor binding / regulation of postsynaptic membrane potential / behavioral fear response / multicellular organismal response to stress / phosphatase binding / D2 dopamine receptor binding / calcium ion homeostasis / synaptic cleft / cellular response to manganese ion / prepulse inhibition / positive regulation of synaptic transmission / detection of mechanical stimulus involved in sensory perception of pain / response to mechanical stimulus / regulation of neuron apoptotic process / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / monoatomic cation channel activity / cellular response to forskolin / sensory perception of pain 類似検索 - 分子機能 Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / リガンド依存性イオンチャネル / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site ... Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / : / リガンド依存性イオンチャネル / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I 類似検索 - ドメイン・相同性 Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2B 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.3 Å 詳細 データ登録者Chou T-H / Furukawa H 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) NS111745 米国 National Institutes of Health/National Institute of Mental Health (NIH/NIMH) MH085926 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2022タイトル : Structural insights into binding of therapeutic channel blockers in NMDA receptors.著者 : Tsung-Han Chou / Max Epstein / Kevin Michalski / Eve Fine / Philip C Biggin / Hiro Furukawa / 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. 履歴 登録 2021年9月22日 - ヘッダ(付随情報) 公開 2022年7月20日 - マップ公開 2022年7月20日 - 更新 2022年7月20日 - 現状 2022年7月20日 処理サイト : RCSB / 状態 : 公開
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