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 mapping of Na1.7 antagonists.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 3224, Year 2023
掲載日	2023年6月3日
著者	Qiurong Wu / Jian Huang / Xiao Fan / Kan Wang / Xueqin Jin / Gaoxingyu Huang / Jiaao Li / Xiaojing Pan / Nieng Yan /
PubMed 要旨	Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in ...Voltage-gated sodium (Na) channels are targeted by a number of widely used and investigational drugs for the treatment of epilepsy, arrhythmia, pain, and other disorders. Despite recent advances in structural elucidation of Na channels, the binding mode of most Na-targeting drugs remains unknown. Here we report high-resolution cryo-EM structures of human Na1.7 treated with drugs and lead compounds with representative chemical backbones at resolutions of 2.6-3.2 Å. A binding site beneath the intracellular gate (site BIG) accommodates carbamazepine, bupivacaine, and lacosamide. Unexpectedly, a second molecule of lacosamide plugs into the selectivity filter from the central cavity. Fenestrations are popular sites for various state-dependent drugs. We show that vinpocetine, a synthetic derivative of a vinca alkaloid, and hardwickiic acid, a natural product with antinociceptive effect, bind to the III-IV fenestration, while vixotrigine, an analgesic candidate, penetrates the IV-I fenestration of the pore domain. Our results permit building a 3D structural map for known drug-binding sites on Na channels summarized from the present and previous structures.
リンク	Nat Commun / PubMed:37270609 / PubMed Central
手法	EM (単粒子)
解像度	2.6 - 3.2 Å
構造データ	35193 8i5b EMDB-35193, PDB-8i5b: Structure of human Nav1.7 in complex with bupivacaine 手法: EM (単粒子) / 解像度: 2.7 Å 35194 8i5g EMDB-35194, PDB-8i5g: Structure of human Nav1.7 in complex with PF-05089771 手法: EM (単粒子) / 解像度: 2.7 Å 35197 8i5x EMDB-35197, PDB-8i5x: Structure of human Nav1.7 in complex with Vinpocetine 手法: EM (単粒子) / 解像度: 2.9 Å 35198 8i5y EMDB-35198, PDB-8i5y: Structure of human Nav1.7 in complex with vixotrigine 手法: EM (単粒子) / 解像度: 2.6 Å 35975 8j4f EMDB-35975, PDB-8j4f: Structure of human Nav1.7 in complex with Hardwickii acid 手法: EM (単粒子) / 解像度: 3.0 Å 40238 8s9b EMDB-40238, PDB-8s9b: Cryo-EM structure of Nav1.7 with LCM 手法: EM (単粒子) / 解像度: 2.9 Å 40239 8s9c EMDB-40239, PDB-8s9c: Cryo-EM structure of Nav1.7 with CBZ 手法: EM (単粒子) / 解像度: 3.2 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 ChemComp-P5S: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine / O-(1-O,2-O-ジステアロイル-L-グリセロ-3-ホスホ)セリン ChemComp-Y01: CHOLESTEROL HEMISUCCINATE / コレステリルヘミスクシナ-ト ChemComp-LPE: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE / O-(1-O-オクタデシル-L-グリセロ-3-ホスホ)コリン ChemComp-PCW: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / O-(1-O,2-O-ジオレオイル-L-グリセロ-3-ホスホ)コリン / DOPC, リン脂質YM ChemComp-OJ0: Levobupivacaine / レボブピバカイン ChemComp-9Z9: (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en / 可溶化剤YM ChemComp-T70: PF-05089771 / PF-05089771 ChemComp-NA: Unknown entry / ナトリウムカチオン ChemComp-HOH: WATER ChemComp-T7F: Vinpocetine / ビンポセチン ChemComp-TB4: Vixotrigine / CNV-1014802 ChemComp-1PW: (2S,3R,4E)-2-(acetylamino)-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate / C₂-セラミド1-ホスファ-ト ChemComp-UK0: (4~{a}~{R},5~{S},6~{R},8~{a}~{R})-5-[2-(furan-3-yl)ethyl]-5,6,8~{a}-trimethyl-3,4,4~{a},6,7,8-hexahydronaphthalene-1-carboxylic acid / (-)-ハ-ドウィッキ酸 ChemComp-LQO: lacosamide / ラコサミド ChemComp-N6W: benzo[b][1]benzazepine-11-carboxamide / カルバマゼピン / 薬剤*YM
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / Inhibitor complex. / Cryo-EM / sodium channel / VGSC / Nav1.7