+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8d76 | ||||||
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タイトル | Crystal Structure of EGFR LRTM with compound 24 | ||||||
要素 | Epidermal growth factor receptor | ||||||
キーワード | SIGNALING PROTEIN / Protein Kinase / inhibitor / kinase domain / mutation | ||||||
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 / tongue development / Inhibition of Signaling by Overexpressed EGFR ...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 / tongue development / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / epidermal growth factor binding / response to UV-A / PLCG1 events in ERBB2 signaling / midgut development / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / response to cobalamin / Signaling by ERBB4 / eyelid development in camera-type eye / 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 / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / cellular response to cadmium ion / EGFR Transactivation by Gastrin / transmembrane receptor protein tyrosine kinase activity / GRB2 events in ERBB2 signaling / positive regulation of DNA repair / SHC1 events in ERBB2 signaling / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / positive regulation of synaptic transmission, glutamatergic / neuron projection morphogenesis / basal plasma membrane / positive regulation of epithelial cell proliferation / epithelial cell proliferation / positive regulation of superoxide anion generation / positive regulation of DNA replication / Signal transduction by L1 / cellular response to estradiol stimulus / liver regeneration / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / positive regulation of protein localization to plasma membrane / Signaling by ERBB2 TMD/JMD mutants / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / EGFR downregulation / lung development / clathrin-coated endocytic vesicle membrane / positive regulation of MAP kinase activity / Constitutive Signaling by EGFRvIII / negative regulation of protein catabolic process / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / receptor protein-tyrosine kinase / kinase binding / Downregulation of ERBB2 signaling / cell-cell adhesion / positive regulation of miRNA transcription / ruffle membrane / HCMV Early Events 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: 2.4 Å | ||||||
データ登録者 | Kim, J.L. | ||||||
資金援助 | 1件
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引用 | ジャーナル: J.Med.Chem. / 年: 2022 タイトル: Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer. 著者: Eno, M.S. / Brubaker, J.D. / Campbell, J.E. / De Savi, C. / Guzi, T.J. / Williams, B.D. / Wilson, D. / Wilson, K. / Brooijmans, N. / Kim, J. / Ozen, A. / Perola, E. / Hsieh, J. / Brown, V. / ...著者: Eno, M.S. / Brubaker, J.D. / Campbell, J.E. / De Savi, C. / Guzi, T.J. / Williams, B.D. / Wilson, D. / Wilson, K. / Brooijmans, N. / Kim, J. / Ozen, A. / Perola, E. / Hsieh, J. / Brown, V. / Fetalvero, K. / Garner, A. / Zhang, Z. / Stevison, F. / Woessner, R. / Singh, J. / Timsit, Y. / Kinkema, C. / Medendorp, C. / Lee, C. / Albayya, F. / Zalutskaya, A. / Schalm, S. / Dineen, T.A. | ||||||
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 | 8d76.cif.gz | 159.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8d76.ent.gz | 122.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8d76.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 | 8d76_validation.pdf.gz | 1012.4 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8d76_full_validation.pdf.gz | 1018.6 KB | 表示 | |
XML形式データ | 8d76_validation.xml.gz | 31.6 KB | 表示 | |
CIF形式データ | 8d76_validation.cif.gz | 47.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/d7/8d76 ftp://data.pdbj.org/pub/pdb/validation_reports/d7/8d76 | HTTPS FTP |
-関連構造データ
関連構造データ | 8d73C 4i22S 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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2 |
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単位格子 |
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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域: Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: LEU / Beg label comp-ID: LEU / End auth comp-ID: ALA / End label comp-ID: ALA / Refine code: _ / Auth seq-ID: 703 - 1013 / Label seq-ID: 29 - 339
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-要素
#1: タンパク質 | 分子量: 39797.777 Da / 分子数: 2 / 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 #2: 化合物 | ChemComp-GOL / #3: 化合物 | #4: 水 | ChemComp-HOH / | 研究の焦点であるリガンドがあるか | Y | |
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-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: 2.14 Å3/Da / 溶媒含有率: 42.45 % |
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結晶化 | 温度: 285 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 8 詳細: 0.1 M sodium acetate pH 5.3, 0.2 M potassium acetate, 3% PEG 8000. |
-データ収集
回折 | 平均測定温度: 110 K / Ambient temp details: 2018-07-18 / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: Diamond / ビームライン: I04-1 / 波長: 0.9159 Å |
検出器 | タイプ: DECTRIS PILATUS 6M-F / 検出器: PIXEL / 日付: 2018年7月18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: 0.9159 Å / 相対比: 1 |
反射 | 解像度: 2.39→48.7 Å / Num. obs: 25531 / % possible obs: 98 % / 冗長度: 3.5 % / Rrim(I) all: 0.08 / Net I/σ(I): 10.8 |
反射 シェル | 解像度: 2.39→2.43 Å / 冗長度: 3.5 % / Mean I/σ(I) obs: 2.2 / Num. unique obs: 1289 / Rrim(I) all: 0.63 / % possible all: 96.9 |
-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: 4i22 解像度: 2.4→30 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.913 / SU B: 11.121 / SU ML: 0.247 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R: 1.161 / ESU R Free: 0.315 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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溶媒の処理 | イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 157.35 Å2 / Biso mean: 61.506 Å2 / Biso min: 33.84 Å2
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精密化ステップ | サイクル: final / 解像度: 2.4→30 Å
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拘束条件 |
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Refine LS restraints NCS | Ens-ID: 1 / 数: 10398 / Refine-ID: X-RAY DIFFRACTION / タイプ: interatomic distance / Rms dev position: 0.05 Å / Weight position: 0.05
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LS精密化 シェル | 解像度: 2.4→2.462 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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