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 basis for Na1.7 inhibition by pore blockers.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 29, Issue 12, Page 1208-1216, Year 2022
掲載日	2022年11月24日
著者	Jiangtao Zhang / Yiqiang Shi / Zhuo Huang / Yue Li / Bei Yang / Jianke Gong / Daohua Jiang /
PubMed 要旨	Voltage-gated sodium channel Na1.7 plays essential roles in pain and odor perception. Na1.7 variants cause pain disorders. Accordingly, Na1.7 has elicited extensive attention in developing new ...Voltage-gated sodium channel Na1.7 plays essential roles in pain and odor perception. Na1.7 variants cause pain disorders. Accordingly, Na1.7 has elicited extensive attention in developing new analgesics. Here we present cryo-EM structures of human Na1.7/β1/β2 complexed with inhibitors XEN907, TC-N1752 and Na1.7-IN2, explaining specific binding sites and modulation mechanism for the pore blockers. These inhibitors bind in the central cavity blocking ion permeation, but engage different parts of the cavity wall. XEN907 directly causes α- to π-helix transition of DIV-S6 helix, which tightens the fast inactivation gate. TC-N1752 induces π-helix transition of DII-S6 helix mediated by a conserved asparagine on DIII-S6, which closes the activation gate. Na1.7-IN2 serves as a pore blocker without causing conformational change. Electrophysiological results demonstrate that XEN907 and TC-N1752 stabilize Na1.7 in inactivated state and delay the recovery from inactivation. Our results provide structural framework for Na1.7 modulation by pore blockers, and important implications for developing subtype-selective analgesics.
リンク	Nat Struct Mol Biol / PubMed:36424527
手法	EM (単粒子)
解像度	3.07 - 3.22 Å
構造データ	33292 7xm9 EMDB-33292: Sodium channel PDB-7xm9: Cryo-EM structure of human NaV1.7/beta1/beta2-XEN907 手法: EM (単粒子) / 解像度: 3.22 Å 33295 7xmf EMDB-33295, PDB-7xmf: Cryo-EM structure of human NaV1.7/beta1/beta2-Nav1.7-IN2 手法: EM (単粒子) / 解像度: 3.07 Å 33296 7xmg EMDB-33296: Sodium channel PDB-7xmg: Cryo-EM structure of human NaV1.7/beta1/beta2-TCN-1752 手法: EM (単粒子) / 解像度: 3.09 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-G2E: (7~{R})-1'-pentylspiro[6~{H}-furo[3,2-f][1,3]benzodioxole-7,3'-indole]-2'-one ChemComp-6OU: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate / POPE / リン脂質YM ChemComp-G2W: 3-[[4-[3-(4-fluoranyl-2-methyl-phenoxy)azetidin-1-yl]pyrimidin-2-yl]amino]-~{N}-methyl-benzamide ChemComp-G4I*: (1~{Z})-~{N}-[2-methyl-3-[(~{E})-[6-[4-[[4-(trifluoromethyloxy)phenyl]methoxy]piperidin-1-yl]-1~{H}-1,3,5-triazin-2-ylidene]amino]phenyl]ethanimidic acid / N-[3-[4-[4-[4-(トリフルオロメトキシ)ベンジルオキシ]ピペリジノ]-1,3,5-トリアジン-2-イルアミ(以下略)
由来	homo sapiens (ヒト) aequorea victoria (オワンクラゲ)
キーワード	TRANSPORT PROTEIN / Sodium channel / PROTEIN TRANSPORT