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 mechanisms of TRPV6 inhibition by ruthenium red and econazole.
ジャーナル・号・ページ	Nat Commun, Vol. 12, Issue 1, Page 6284, Year 2021
掲載日	2021年11月1日
著者	Arthur Neuberger / Kirill D Nadezhdin / Alexander I Sobolevsky /
PubMed 要旨	TRPV6 is a calcium-selective ion channel implicated in epithelial Ca uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, ...TRPV6 is a calcium-selective ion channel implicated in epithelial Ca uptake. TRPV6 inhibitors are needed for the treatment of a broad range of diseases associated with disturbed calcium homeostasis, including cancers. Here we combine cryo-EM, calcium imaging, and mutagenesis to explore molecular bases of human TRPV6 inhibition by the antifungal drug econazole and the universal ion channel blocker ruthenium red (RR). Econazole binds to an allosteric site at the channel's periphery, where it replaces a lipid. In contrast, RR inhibits TRPV6 by binding in the middle of the ion channel's selectivity filter and plugging its pore like a bottle cork. Despite different binding site locations, both inhibitors induce similar conformational changes in the channel resulting in closure of the gate formed by S6 helices bundle crossing. The uncovered molecular mechanisms of TRPV6 inhibition can guide the design of a new generation of clinically useful inhibitors.
リンク	Nat Commun / PubMed:34725357 / PubMed Central
手法	EM (単粒子)
解像度	2.43 - 2.85 Å
構造データ	24890 7s88 EMDB-24890, PDB-7s88: Open apo-state cryo-EM structure of human TRPV6 in glyco-diosgenin detergent 手法: EM (単粒子) / 解像度: 2.69 Å 24891 7s89 EMDB-24891, PDB-7s89: Open apo-state cryo-EM structure of human TRPV6 in cNW11 nanodiscs 手法: EM (単粒子) / 解像度: 2.54 Å 24892 7s8b EMDB-24892, PDB-7s8b: Cryo-EM structure of human TRPV6 in complex with channel blocker ruthenium red 手法: EM (単粒子) / 解像度: 2.43 Å 24893 7s8c EMDB-24893, PDB-7s8c: Cryo-EM structure of human TRPV6 in complex with inhibitor econazole 手法: EM (単粒子) / 解像度: 2.85 Å
化合物	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE / コレステリルヘミスクシナ-ト 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-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM / POホスファチジルコリン ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-HOH: WATER / 水 ChemComp-R2R: ruthenium(6+) azanide pentaamino(oxido)ruthenium (1/4/2) / Ruthenium red ChemComp-ECL: 1-[(2R)-2-[(4-chlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole / 1-[(βR)-β-(4-クロロベンジルオキシ)-2,4-ジクロロフェネチル]-1H-イミダゾ-ル ChemComp-CL: Unknown entry / クロリド / 塩化物
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / Transient Receptor Potential V Family Member 6 / TRP / channel / apo / open / human (ヒト) / TRPV6 / cNW11 / nanodiscs / ruthenium red / channel blocker / antagonist (受容体拮抗薬) / econazole / inhibitor (酵素阻害剤)