登録情報 データベース : EMDB / ID : EMD-7073 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide マップデータlow-pass filtered and sharpened with B-factor of -50, pancreatic beta-cell KATP channel bound to ATP and glibenclamide 詳細 試料複合体 : Pancreatic beta-cell ATP-sensitive K+ channel (KATP)複合体 : ATP-sensitive K+ channel subunit Kir6.2タンパク質・ペプチド : ATP-sensitive inward rectifier potassium channel 11複合体 : ATP-binding cassette sub-family C member 8タンパク質・ペプチド : ATP-binding cassette sub-family C member 8リガンド : ADENOSINE-5'-TRIPHOSPHATEリガンド : 5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide 詳細機能・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
Regulation of insulin secretion / ATP感受性カリウムチャネル / ABC-family proteins mediated transport / response to resveratrol / ventricular cardiac muscle tissue development / ATP-activated inward rectifier potassium channel activity / cell body fiber / inward rectifying potassium channel / sulfonylurea receptor activity / CAMKK-AMPK signaling cascade ... Regulation of insulin secretion / ATP感受性カリウムチャネル / ABC-family proteins mediated transport / response to resveratrol / ventricular cardiac muscle tissue development / ATP-activated inward rectifier potassium channel activity / cell body fiber / inward rectifying potassium channel / sulfonylurea receptor activity / CAMKK-AMPK signaling cascade / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / 活動電位 / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / potassium ion import across plasma membrane / voltage-gated potassium channel activity / potassium channel activity / regulation of insulin secretion / axolemma / 介在板 / negative regulation of insulin secretion / ABC-type transporter activity / potassium ion transmembrane transport / 横行小管 / heat shock protein binding / regulation of membrane potential / acrosomal vesicle / response to ischemia / determination of adult lifespan / cellular response to glucose stimulus / positive regulation of protein localization to plasma membrane / 筋鞘 / potassium ion transport / cellular response to nicotine / glucose metabolic process / response to estradiol / presynaptic membrane / 核膜 / cellular response to tumor necrosis factor / transmembrane transporter binding / response to hypoxia / エンドソーム / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / 細胞膜 類似検索 - 分子機能 Potassium channel, inwardly rectifying, Kir6.2 / ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / Potassium channel, inwardly rectifying, transmembrane domain / Inward rectifier potassium channel transmembrane domain / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / Inward rectifier potassium channel, C-terminal / Inward rectifier potassium channel C-terminal domain / ABC transporter transmembrane region ... Potassium channel, inwardly rectifying, Kir6.2 / ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / Potassium channel, inwardly rectifying, transmembrane domain / Inward rectifier potassium channel transmembrane domain / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / Inward rectifier potassium channel, C-terminal / Inward rectifier potassium channel C-terminal domain / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / Immunoglobulin E-set / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 ATP-sensitive inward rectifier potassium channel 11 / ATP-binding cassette sub-family C member 8 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ) / Cricetus cricetus (クロハラハムスクー)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.63 Å 詳細 データ登録者Martin GM / Yoshioka C / Shyng SL 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK) 米国
引用ジャーナル : Elife / 年 : 2017タイトル : Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM.著者 : Gregory M Martin / Balamurugan Kandasamy / Frank DiMaio / Craig Yoshioka / Show-Ling Shyng / 要旨 : Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been ... Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the K channel complex to inhibit channel activity. 履歴 登録 2017年10月12日 - ヘッダ(付随情報) 公開 2017年11月1日 - マップ公開 2017年11月1日 - 更新 2019年12月25日 - 現状 2019年12月25日 処理サイト : RCSB / 状態 : 公開
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