登録情報 データベース : PDB / ID : 6o2p 構造の表示 ダウンロードとリンクタイトル Complex of ivacaftor with cystic fibrosis transmembrane conductance regulator (CFTR) 要素Cystic fibrosis transmembrane conductance regulator Unknown Peptide 詳細キーワード HYDROLASE / ABC transporter / anion channel / cystic fibrosis / membrane protein / ivacaftor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 voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis ... positive regulation of voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis / chloride channel inhibitor activity / ATPase-coupled inorganic anion transmembrane transporter activity / Golgi-associated vesicle membrane / multicellular organismal-level water homeostasis / membrane hyperpolarization / cholesterol transport / bicarbonate transport / bicarbonate transmembrane transporter activity / vesicle docking involved in exocytosis / chloride channel regulator activity / chloride transmembrane transporter activity / sperm capacitation / chloride channel activity / RHOQ GTPase cycle / cholesterol biosynthetic process / positive regulation of exocytosis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / chloride channel complex / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / cellular response to cAMP / cellular response to forskolin / chloride transmembrane transport / isomerase activity / response to endoplasmic reticulum stress / establishment of localization in cell / PDZ domain binding / Defective CFTR causes cystic fibrosis / Late endosomal microautophagy / clathrin-coated endocytic vesicle membrane / ABC-family proteins mediated transport / recycling endosome / transmembrane transport / Aggrephagy / Chaperone Mediated Autophagy / recycling endosome membrane / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / early endosome membrane / protein-folding chaperone binding / early endosome / endosome membrane / Ub-specific processing proteases / apical plasma membrane / lysosomal membrane / endoplasmic reticulum membrane / enzyme binding / cell surface / ATP hydrolysis activity / protein-containing complex / ATP binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 : / CFTR regulator domain / Cystic fibrosis TM conductance regulator (CFTR), regulator domain / Cystic fibrosis transmembrane conductance regulator / 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. ... : / CFTR regulator domain / Cystic fibrosis TM conductance regulator (CFTR), regulator domain / Cystic fibrosis transmembrane conductance regulator / 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. / 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 ADENOSINE-5'-TRIPHOSPHATE / Chem-POV / Chem-VX7 / Cystic fibrosis transmembrane conductance regulator 類似検索 - 構成要素生物種 Homo sapiens (ヒト)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 : 3.3 Å 詳細データ登録者 Liu, F. / Zhang, Z. / Chen, J. / Levit, A. / Shoichet, B. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 Howard Hughes Medical Institute (HHMI) 米国
引用ジャーナル : Science / 年 : 2019タイトル : Structural identification of a hotspot on CFTR for potentiation.著者 : Fangyu Liu / Zhe Zhang / Anat Levit / Jesper Levring / Kouki K Touhara / Brian K Shoichet / Jue Chen / 要旨 : Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve ... Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)-approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds. 履歴 登録 2019年2月24日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年6月26日 Provider : repository / タイプ : Initial release改定 1.1 2019年7月3日 Group : Data collection / Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name 改定 1.2 2019年11月20日 Group : Author supporting evidence / カテゴリ : pdbx_audit_support / Item : _pdbx_audit_support.funding_organization改定 1.3 2019年11月27日 Group : Data collection / カテゴリ : em_software / Item : _em_software.name改定 2.0 2021年8月25日 Group : Advisory / Atomic model ... Advisory / Atomic model / Data collection / Database references カテゴリ : atom_site / database_2 ... atom_site / database_2 / database_PDB_caveat / pdbx_unobs_or_zero_occ_atoms / pdbx_validate_chiral Item : _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ... _atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_atom_id / _atom_site.label_atom_id / _atom_site.type_symbol / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_unobs_or_zero_occ_atoms.auth_atom_id / _pdbx_unobs_or_zero_occ_atoms.label_atom_id 改定 2.1 2024年5月15日 Group : Data collection / Refinement descriptionカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / em_3d_fitting_list / pdbx_initial_refinement_model Item : _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id ... _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type
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