登録情報 データベース : PDB / ID : 6baa 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 要素ATP-binding cassette sub-family C member 8 ATP-sensitive inward rectifier potassium channel 11 詳細キーワード METAL TRANSPORT / KATP / SUR1 / Kir6.2 / sulfonylurea receptor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 sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / cell body fiber / CAMKK-AMPK signaling cascade ... Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / cell body fiber / 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 / regulation of monoatomic ion transmembrane transport / nervous system process / inorganic cation transmembrane transport / ankyrin binding / Ion homeostasis / response to ATP / response to stress / potassium ion import across plasma membrane / response to testosterone / action potential / voltage-gated potassium channel activity / axolemma / intercalated disc / potassium channel activity / ABC-type transporter activity / cellular response to nutrient levels / negative regulation of insulin secretion / heat shock protein binding / potassium ion transmembrane transport / T-tubule / regulation of insulin secretion / acrosomal vesicle / response to ischemia / regulation of membrane potential / determination of adult lifespan / positive regulation of protein localization to plasma membrane / cellular response to glucose stimulus / potassium ion transport / sarcolemma / cellular response to nicotine / glucose metabolic process / nuclear envelope / cellular response to tumor necrosis factor / response to estradiol / presynaptic membrane / transmembrane transporter binding / response to hypoxia / endosome / response to xenobiotic stimulus / neuronal cell body / apoptotic process / glutamatergic synapse / protein-containing complex / ATP hydrolysis activity / ATP binding / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 G protein-activated inward rectifier potassium channel 1 / 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 ... G protein-activated inward rectifier potassium channel 1 / 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 / : / Helix Hairpins - #70 / 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. / Helix Hairpins / Immunoglobulin E-set / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Immunoglobulin-like / Sandwich / P-loop containing nucleoside triphosphate hydrolase / Orthogonal Bundle / Mainly Beta / Mainly Alpha 類似検索 - ドメイン・相同性 ADENOSINE-5'-TRIPHOSPHATE / Chem-GBM / 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 電子顕微鏡法 / 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, G.M. / Yoshioka, C. / Shyng, S.L. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 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 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2017年11月1日 Provider : repository / タイプ : Initial release改定 1.1 2018年2月28日 Group : Database references / カテゴリ : citation / Item : _citation.title改定 1.2 2018年3月28日 Group : Data collection / Database references / カテゴリ : citation / Item : _citation.title改定 1.3 2019年12月25日 Group : Author supporting evidence / カテゴリ : pdbx_audit_support / Item : _pdbx_audit_support.funding_organization改定 1.4 2024年11月20日 Group : Data collection / Database references / Structure summaryカテゴリ : chem_comp / chem_comp_atom ... chem_comp / chem_comp_atom / chem_comp_bond / database_2 / em_admin / pdbx_entry_details / pdbx_modification_feature Item : _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ... _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_admin.last_update
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