+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7vra | ||||||
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タイトル | The crystal structure of EGFR T790M/C797S with the inhibitor HC5476 | ||||||
要素 | Epidermal growth factor receptor | ||||||
キーワード | TRANSFERASE/TRANSFERASE INHIBITOR / EGFR / inhibitor / complex / 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: 2.41 Å | ||||||
データ登録者 | Zhu, S.J. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: J.Med.Chem. / 年: 2022 タイトル: Conformational Constrained 4-(1-Sulfonyl-3-indol)yl-2-phenylaminopyrimidine Derivatives as New Fourth-Generation Epidermal Growth Factor Receptor Inhibitors Targeting T790M/C797S Mutations. 著者: Chen, H. / Lai, M. / Zhang, T. / Chen, Y. / Tong, L. / Zhu, S. / Zhou, Y. / Ren, X. / Ding, J. / Xie, H. / Lu, X. / Ding, K. | ||||||
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 | 7vra.cif.gz | 76.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7vra.ent.gz | 54.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7vra.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 | 7vra_validation.pdf.gz | 815.5 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7vra_full_validation.pdf.gz | 819.2 KB | 表示 | |
XML形式データ | 7vra_validation.xml.gz | 13.2 KB | 表示 | |
CIF形式データ | 7vra_validation.cif.gz | 17 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vr/7vra ftp://data.pdbj.org/pub/pdb/validation_reports/vr/7vra | HTTPS FTP |
-関連構造データ
関連構造データ | 7vreC 6jrjS 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: 37460.363 Da / 分子数: 1 / 変異: T790M, C797S / 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 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-I0A / |
#3: 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: 3.39 Å3/Da / 溶媒含有率: 63.71 % |
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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: 6.2 詳細: 0.05M CaCl2, 0.1M B-Tris pH 6.2, 24% PEG 550MME, 5mM TCEP |
-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: SSRF / ビームライン: BL19U1 / 波長: 0.987 Å |
検出器 | タイプ: DECTRIS PILATUS 300K / 検出器: PIXEL / 日付: 2020年11月28日 |
放射 | 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: 0.987 Å / 相対比: 1 |
反射 | 解像度: 2.41→50 Å / Num. obs: 19296 / % possible obs: 100 % / 冗長度: 19.3 % / Rpim(I) all: 0.029 / Net I/σ(I): 41 |
反射 シェル | 解像度: 2.41→2.5 Å / Num. unique obs: 19296 / Rpim(I) all: 0.479 |
-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: 6JRJ 解像度: 2.41→22.37 Å / SU ML: 0.35 / 交差検証法: THROUGHOUT / σ(F): 1.34 / 位相誤差: 31.2 / 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: 138.03 Å2 / Biso mean: 66.3609 Å2 / Biso min: 38.38 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 2.41→22.37 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: 7
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