EMDB/PDB/SASBDBから引用されている文献のデータベース

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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 of the Modulation of the Voltage-Gated Calcium Ion Channel Ca 1.1 by Dihydropyridine Compounds*.
ジャーナル・号・ページ	Angew Chem Int Ed Engl, Vol. 60, Issue 6, Page 3131-3137, Year 2021
掲載日	2021年2月8日
著者	Shuai Gao / Nieng Yan /
PubMed 要旨	1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca (Ca ) channels. DHP compounds exhibit chirality-specific antagonistic or ...1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca (Ca ) channels. DHP compounds exhibit chirality-specific antagonistic or agonistic effects. The structure of rabbit Ca 1.1 bound to an achiral drug nifedipine reveals the general binding mode for DHP drugs, but the molecular basis for chiral specificity remained elusive. Herein, we report five cryo-EM structures of nanodisc-embedded Ca 1.1 in the presence of the bestselling drug amlodipine, a DHP antagonist (R)-(+)-Bay K8644, and a titration of its agonistic enantiomer (S)-(-)-Bay K8644 at resolutions of 2.9-3.4 Å. The amlodipine-bound structure reveals the molecular basis for the high efficacy of the drug. All structures with the addition of the Bay K8644 enantiomers exhibit similar inactivated conformations, suggesting that (S)-(-)-Bay K8644, when acting as an agonist, is insufficient to lock the activated state of the channel for a prolonged duration.
リンク	Angew Chem Int Ed Engl / PubMed:33125829 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 3.4 Å
構造データ	22414 7jpk EMDB-22414, PDB-7jpk: Rabbit Cav1.1 in the presence of 100 micromolar (S)-(-)-Bay K8644 in nanodiscs at 3.0 Angstrom resolution 手法: EM (単粒子) / 解像度: 3.0 Å 22415 7jpl EMDB-22415, PDB-7jpl: Rabbit Cav1.1 in the presence of 10 micromolar (S)-(-)-Bay K8644 in nanodiscs at 3.4 Angstrom resolution 手法: EM (単粒子) / 解像度: 3.4 Å 22424 7jpv EMDB-22424, PDB-7jpv: Rabbit Cav1.1 in the presence of 1 micromolar (S)-(-)-Bay K8644 in nanodiscs at 3.4 Angstrom resolution 手法: EM (単粒子) / 解像度: 3.4 Å 22425 7jpw EMDB-22425, PDB-7jpw: Rabbit Cav1.1 in the presence of 100 micromolar (R)-(+)-Bay K8644 in nanodiscs at 3.2 Angstrom resolution 手法: EM (単粒子) / 解像度: 3.2 Å 22426 7jpx EMDB-22426, PDB-7jpx: Rabbit Cav1.1 in the presence of 100 micromolar amlodipine in nanodiscs at 2.9 Angstrom resolution 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-3PE: 1,2-Distearoyl-sn-glycerophosphoethanolamine / DSPE / リン脂質YM / ホスファチジルエタノールアミン ChemComp-PC1: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / リン脂質YM / ホスファチジルコリン ChemComp-C8U: methyl (4~{S})-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate ChemComp-VFY: methyl (4~{R})-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate 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-6UB: amlodipine / (S)-アムロジピン / チャネルブロッカーYM / Levamlodipine
由来	oryctolagus cuniculus (ウサギ) Rabbit (ウサギ)
キーワード	TRANSPORT PROTEIN (運搬体タンパク質) / rCav1.1 / Channels; Calcium Ion-Selective / drugs (薬物) / Channels / Calcium Ion-Selective