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 / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration ... neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / regulation of postsynaptic cytosolic calcium ion concentration / sensory organ development / sensitization / 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 / response to hydrogen sulfide / Assembly and cell surface presentation of NMDA receptors / olfactory learning / regulation of protein kinase A signaling / conditioned taste aversion / apical dendrite / regulation of respiratory gaseous exchange / dendritic branch / positive regulation of inhibitory postsynaptic potential / response to other organism / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / response to methylmercury / fear response / propylene metabolic process / response to glycine / positive regulation of cysteine-type endopeptidase activity / cellular response to dsRNA / response to carbohydrate / negative regulation of dendritic spine maintenance / interleukin-1 receptor binding / voltage-gated monoatomic cation channel activity / cellular response to lipid / regulation of monoatomic cation transmembrane transport / positive regulation of glutamate secretion / response to growth hormone / NMDA glutamate receptor activity / Synaptic adhesion-like molecules / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to manganese ion / NMDA selective glutamate receptor signaling pathway / response to morphine / calcium ion transmembrane import into cytosol / neuromuscular process / glutamate binding / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / regulation of axonogenesis / regulation of dendrite morphogenesis / positive regulation of calcium ion transport into cytosol / male mating behavior / glycine binding / heterocyclic compound binding / receptor clustering / suckling behavior / startle response / response to amine / small molecule binding / : / action potential / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / monoatomic cation transport / behavioral response to pain / associative learning / regulation of MAPK cascade / social behavior / response to magnesium ion / cellular response to organic cyclic compound / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / extracellularly glutamate-gated ion channel activity / cellular response to glycine / excitatory synapse / positive regulation of dendritic spine maintenance / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / phosphatase binding / behavioral fear response / neuron development / postsynaptic density, intracellular component / cellular response to manganese ion / glutamate receptor binding / multicellular organismal response to stress / long-term memory / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition / D2 dopamine receptor binding / monoatomic cation channel activity / calcium ion homeostasis / regulation of neuron apoptotic process / response to electrical stimulus / synaptic cleft / response to mechanical stimulus / glutamate-gated receptor activity 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 / : / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain ... 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 / : / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / 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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