+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7u9a | |||||||||
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タイトル | EGFR in complex with a macrocyclic inhibitor | |||||||||
要素 | Epidermal growth factor receptor | |||||||||
キーワード | TRANSFERASE/TRANSFERASE INHIBITOR / EGFR / kinase / macrocycle / inhibitor / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex | |||||||||
機能・相同性 | 機能・相同性情報 response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity ...response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / eyelid development in camera-type eye / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / cellular response to cadmium ion / positive regulation of DNA repair / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / positive regulation of synaptic transmission, glutamatergic / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / basal plasma membrane / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of DNA replication / epithelial cell proliferation / Signal transduction by L1 / positive regulation of epithelial cell proliferation / cellular response to estradiol stimulus / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / liver regeneration / positive regulation of protein localization to plasma membrane / EGFR downregulation / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / lung development / clathrin-coated endocytic vesicle membrane / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / Downregulation of ERBB2 signaling / kinase binding / ruffle membrane / positive regulation of miRNA transcription / cell-cell adhesion 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 2.6 Å | |||||||||
データ登録者 | Beyett, T.S. / Eck, M.J. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: J.Med.Chem. / 年: 2022 タイトル: Macrocyclization of Quinazoline-Based EGFR Inhibitors Leads to Exclusive Mutant Selectivity for EGFR L858R and Del19. 著者: Amrhein, J.A. / Beyett, T.S. / Feng, W.W. / Kramer, A. / Weckesser, J. / Schaeffner, I.K. / Rana, J.K. / Janne, P.A. / Eck, M.J. / Knapp, S. / Hanke, T. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7u9a.cif.gz | 138.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7u9a.ent.gz | 106.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7u9a.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7u9a_validation.pdf.gz | 720.3 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7u9a_full_validation.pdf.gz | 726.5 KB | 表示 | |
XML形式データ | 7u9a_validation.xml.gz | 13.8 KB | 表示 | |
CIF形式データ | 7u9a_validation.cif.gz | 17.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/u9/7u9a ftp://data.pdbj.org/pub/pdb/validation_reports/u9/7u9a | HTTPS FTP |
-関連構造データ
関連構造データ | 7u98C 7u99C 6vhpS S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 37636.441 Da / 分子数: 1 / 断片: kinase domain, residues 695-1022 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EGFR, ERBB, ERBB1, HER1 / プラスミド: pTriEX / 細胞株 (発現宿主): Sf9 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P00533, receptor protein-tyrosine kinase |
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#2: 化合物 | ChemComp-M19 / |
#3: 化合物 | ChemComp-FLC / |
#4: 水 | ChemComp-HOH / |
研究の焦点であるリガンドがあるか | Y |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 3.43 Å3/Da / 溶媒含有率: 64.17 % / Mosaicity: 0.053 ° |
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結晶化 | 温度: 293 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 6.5 / 詳細: 0.1 M MES pH 6.5, 1.1 M Sodium Citrate |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||
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放射光源 | 由来: シンクロトロン / サイト: APS / ビームライン: 24-ID-C / 波長: 0.97918 Å | ||||||||||||||||||||||||
検出器 | タイプ: DECTRIS EIGER X 16M / 検出器: PIXEL / 日付: 2021年7月23日 | ||||||||||||||||||||||||
放射 | モノクロメーター: Double Crystal / プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray | ||||||||||||||||||||||||
放射波長 | 波長: 0.97918 Å / 相対比: 1 | ||||||||||||||||||||||||
反射 | 解像度: 2.6→103.11 Å / Num. obs: 16002 / % possible obs: 99.9 % / 冗長度: 5 % / Biso Wilson estimate: 64.33 Å2 / Rpim(I) all: 0.055 / Rrim(I) all: 0.125 / Net I/σ(I): 10.4 / Num. measured all: 80669 | ||||||||||||||||||||||||
反射 シェル | Diffraction-ID: 1
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-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: 6VHP 解像度: 2.6→103.11 Å / SU ML: 0.37 / 交差検証法: THROUGHOUT / σ(F): 1.36 / 位相誤差: 28.05 / 立体化学のターゲット値: ML
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 163.22 Å2 / Biso mean: 69.2666 Å2 / Biso min: 30 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 2.6→103.11 Å
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 5 / % reflection obs: 100 %
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精密化 TLS | 手法: refined / Refine-ID: X-RAY DIFFRACTION
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精密化 TLSグループ |
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