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-基本情報
登録情報 | データベース: PDB / ID: 8bhm | ||||||
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タイトル | GABA-A receptor a5 homomer - a5V3 - DMCM | ||||||
要素 | Gamma-aminobutyric acid receptor subunit alpha-5 | ||||||
キーワード | MEMBRANE PROTEIN (膜タンパク質) / pLGIC GABA Neurotransmission | ||||||
機能・相同性 | 機能・相同性情報 benzodiazepine receptor activity / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / inner ear receptor cell development / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / GABA receptor binding / 神経 ...benzodiazepine receptor activity / inhibitory extracellular ligand-gated monoatomic ion channel activity / GABA receptor activation / inner ear receptor cell development / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / GABA receptor binding / 神経 / synaptic transmission, GABAergic / postsynaptic specialization membrane / gamma-aminobutyric acid signaling pathway / neuronal cell body membrane / cochlea development / transmembrane transporter complex / 学習 / chloride channel complex / GABA-ergic synapse / regulation of postsynaptic membrane potential / behavioral fear response / chloride transmembrane transport / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / presynaptic membrane / signaling receptor activity / postsynapse / neuron projection / シナプス / シグナル伝達 / 核質 / 細胞膜 / 細胞質基質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.95 Å | ||||||
データ登録者 | Miller, P.S. / Malinauskas, T.M. / Hardwick, S.W. / Chirgadze, D.Y. | ||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2023 タイトル: The molecular basis of drug selectivity for α5 subunit-containing GABA receptors. 著者: Vikram Babu Kasaragod / Tomas Malinauskas / Ayla A Wahid / Judith Lengyel / Frederic Knoflach / Steven W Hardwick / Charlotte F Jones / Wan-Na Chen / Xavier Lucas / Kamel El Omari / Dimitri Y ...著者: Vikram Babu Kasaragod / Tomas Malinauskas / Ayla A Wahid / Judith Lengyel / Frederic Knoflach / Steven W Hardwick / Charlotte F Jones / Wan-Na Chen / Xavier Lucas / Kamel El Omari / Dimitri Y Chirgadze / A Radu Aricescu / Giuseppe Cecere / Maria-Clemencia Hernandez / Paul S Miller / 要旨: α5 subunit-containing γ-aminobutyric acid type A (GABA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to ...α5 subunit-containing γ-aminobutyric acid type A (GABA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to neurodevelopmental disorders such as Dup15q and Angelman syndromes, developmental epilepsy and autism. Effective drug action without side effects is dependent on both α5-subtype selectivity and the strength of the positive or negative allosteric modulation (PAM or NAM). Here we solve structures of drugs bound to the α5 subunit. These define the molecular basis of binding and α5 selectivity of the β-carboline, methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), type II benzodiazepine NAMs, and a series of isoxazole NAMs and PAMs. For the isoxazole series, each molecule appears as an 'upper' and 'lower' moiety in the pocket. Structural data and radioligand binding data reveal a positional displacement of the upper moiety containing the isoxazole between the NAMs and PAMs. Using a hybrid molecule we directly measure the functional contribution of the upper moiety to NAM versus PAM activity. Overall, these structures provide a framework by which to understand distinct modulator binding modes and their basis of α5-subtype selectivity, appreciate structure-activity relationships, and empower future structure-based drug design campaigns. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8bhm.cif.gz | 795.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8bhm.ent.gz | 541 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8bhm.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/bh/8bhm ftp://data.pdbj.org/pub/pdb/validation_reports/bh/8bhm | HTTPS FTP |
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-関連構造データ
関連構造データ | 16060MC 8bejC 8bgiC 8bhaC 8bhbC 8bhgC 8bhiC 8bhkC 8bhoC 8bhqC 8bhrC 8bhsC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
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