登録情報 データベース : EMDB / ID : EMD-9867 構造の表示 ダウンロードとリンクタイトル Rabbit Cav1.1-Bay K8644 Complex マップデータEM map 詳細 試料複合体 : Cav1.1-drug complex複合体 : Cav1.1-beta1a-alpha2-delta1-gamma complexタンパク質・ペプチド : Voltage-dependent calcium channel gamma-1 subunitタンパク質・ペプチド : Voltage-dependent L-type calcium channel subunit beta-1タンパク質・ペプチド : Voltage-dependent L-type calcium channel subunit alpha-1Sタンパク質・ペプチド : Voltage-dependent calcium channel subunit alpha-2/delta-1リガンド : methyl (4~{S})-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylateリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : CALCIUM IONリガンド : ETHANOLAMINE 詳細 キーワード Membrane protein complex modulated by FDA approved drug. / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium channel regulator activity / calcium ion import across plasma membrane / voltage-gated calcium channel activity / release of sequestered calcium ion into cytosol / regulation of ryanodine-sensitive calcium-release channel activity ... positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium channel regulator activity / calcium ion import across plasma membrane / voltage-gated calcium channel activity / release of sequestered calcium ion into cytosol / regulation of ryanodine-sensitive calcium-release channel activity / T-tubule / muscle contraction / calcium ion transmembrane transport / sarcolemma / transmembrane transporter binding / calmodulin binding / metal ion binding / plasma membrane 類似検索 - 分子機能 Voltage-dependent calcium channel, L-type, beta-1 subunit / Voltage-dependent calcium channel, gamma-1 subunit / Voltage-dependent calcium channel, L-type, alpha-1S subunit / PMP-22/EMP/MP20/Claudin tight junction / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit ... Voltage-dependent calcium channel, L-type, beta-1 subunit / Voltage-dependent calcium channel, gamma-1 subunit / Voltage-dependent calcium channel, L-type, alpha-1S subunit / PMP-22/EMP/MP20/Claudin tight junction / Voltage-dependent L-type calcium channel subunit beta-1-4, N-terminal A domain / Voltage-dependent calcium channel, L-type, beta subunit / Voltage gated calcium channel subunit beta domain 4Aa N terminal / Voltage-gated calcium channel subunit alpha, C-terminal / Voltage-gated calcium channel subunit alpha, C-term / Voltage-dependent calcium channel, L-type, alpha-1 subunit / VWA N-terminal / Voltage-dependent calcium channel, alpha-2/delta subunit, conserved region / VWA N-terminal / Neuronal voltage-dependent calcium channel alpha 2acd / Voltage-dependent calcium channel, alpha-1 subunit, IQ domain / Voltage gated calcium channel IQ domain / Voltage gated calcium channel IQ domain / Voltage-dependent calcium channel, alpha-1 subunit / Voltage-dependent L-type calcium channel, IQ-associated domain / Voltage-dependent L-type calcium channel, IQ-associated / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / Guanylate kinase/L-type calcium channel beta subunit / Guanylate kinase / Guanylate kinase homologues. / von Willebrand factor type A domain / von Willebrand factor (vWF) type A domain / VWFA domain profile. / Voltage-dependent channel domain superfamily / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Ion transport domain / Ion transport protein / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Voltage-dependent L-type calcium channel subunit alpha-1S / Voltage-dependent calcium channel subunit alpha-2/delta-1 / Voltage-dependent L-type calcium channel subunit beta-1 / Voltage-dependent calcium channel gamma-1 subunit 類似検索 - 構成要素生物種 Oryctolagus cuniculus (ウサギ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.7 Å 詳細 データ登録者Zhao Y / Huang G 資金援助 中国, 6件 詳細 詳細を隠すOrganization Grant number 国 Ministry of Science and Technology (China) 2016YFA0500402 中国 Ministry of Science and Technology (China) 2015CB910101 中国 National Natural Science Foundation of China 31621092 中国 National Natural Science Foundation of China 31630017 中国 National Natural Science Foundation of China 81861138009 中国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R01GM130762 中国
引用ジャーナル : Cell / 年 : 2019タイトル : Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca Channel.著者 : Yanyu Zhao / Gaoxingyu Huang / Jianping Wu / Qiurong Wu / Shuai Gao / Zhen Yan / Jianlin Lei / Nieng Yan / 要旨 : The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been ... The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been used for characterizing channel properties and for treatment of hypertension and other disorders. Here, we report the cryoelectron microscopy (cryo-EM) structures of Ca1.1 in complex with archetypal antagonistic drugs, nifedipine, diltiazem, and verapamil, at resolutions of 2.9 Å, 3.0 Å, and 2.7 Å, respectively, and with a DHP agonist Bay K 8644 at 2.8 Å. Diltiazem and verapamil traverse the central cavity of the pore domain, directly blocking ion permeation. Although nifedipine and Bay K 8644 occupy the same fenestration site at the interface of repeats III and IV, the coordination details support previous functional observations that Bay K 8644 is less favored in the inactivated state. These structures elucidate the modes of action of different Ca ligands and establish a framework for structure-guided drug discovery. 履歴 登録 2019年3月26日 - ヘッダ(付随情報) 公開 2019年5月1日 - マップ公開 2019年6月12日 - 更新 2023年11月15日 - 現状 2023年11月15日 処理サイト : PDBj / 状態 : 公開
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