+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8a2a | ||||||
---|---|---|---|---|---|---|---|
タイトル | EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-1-oxo-4-(trifluoromethyl)isoindolin-2-yl]-N-thiazol-2-yl-acetamide (form 2) | ||||||
要素 | Epidermal growth factor receptor | ||||||
キーワード | TRANSFERASE / KINASE INHIBITOR | ||||||
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: 1.43 Å | ||||||
データ登録者 | Kuglstatter, A. / Ehler, A. | ||||||
資金援助 | スイス, 1件
| ||||||
引用 | ジャーナル: J.Med.Chem. / 年: 2022 タイトル: Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib. 著者: Obst-Sander, U. / Ricci, A. / Kuhn, B. / Friess, T. / Koldewey, P. / Kuglstatter, A. / Hewings, D. / Goergler, A. / Steiner, S. / Rueher, D. / Imhoff, M.P. / Raschetti, N. / Marty, H.P. / ...著者: Obst-Sander, U. / Ricci, A. / Kuhn, B. / Friess, T. / Koldewey, P. / Kuglstatter, A. / Hewings, D. / Goergler, A. / Steiner, S. / Rueher, D. / Imhoff, M.P. / Raschetti, N. / Marty, H.P. / Dietzig, A. / Rynn, C. / Ehler, A. / Burger, D. / Kornacker, M. / Schaffland, J.P. / Herting, F. / Pao, W. / Bischoff, J.R. / Martoglio, B. / Alice Nagel, Y. / Jaeschke, G. | ||||||
履歴 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8a2a.cif.gz | 145.1 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8a2a.ent.gz | 110.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8a2a.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 | 8a2a_validation.pdf.gz | 755.9 KB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 8a2a_full_validation.pdf.gz | 761.2 KB | 表示 | |
XML形式データ | 8a2a_validation.xml.gz | 16.1 KB | 表示 | |
CIF形式データ | 8a2a_validation.cif.gz | 23.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/a2/8a2a ftp://data.pdbj.org/pub/pdb/validation_reports/a2/8a2a | HTTPS FTP |
-関連構造データ
関連構造データ | 8a27SC 8a2bC 8a2dC S: 精密化の開始モデル C: 同じ文献を引用 (文献) |
---|---|
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 |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
単位格子 |
|
-要素
#1: タンパク質 | 分子量: 37225.098 Da / 分子数: 1 / 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-KY9 / ( |
#3: 化合物 | ChemComp-SO4 / |
#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 |
---|
-試料調製
結晶 | マシュー密度: 2.27 Å3/Da / 溶媒含有率: 45.74 % |
---|---|
結晶化 | 温度: 293 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 5.5 詳細: 25% PEG Smear Medium, 0.1 M sodium cacodylate, 0.2 M ammonium sulfate |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
---|---|
放射光源 | 由来: シンクロトロン / サイト: SLS / ビームライン: X10SA / 波長: 0.9999 Å |
検出器 | タイプ: DECTRIS PILATUS 6M / 検出器: PIXEL / 日付: 2019年9月1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: 0.9999 Å / 相対比: 1 |
反射 | 解像度: 1.43→68.59 Å / Num. obs: 40957 / % possible obs: 94.5 % / 冗長度: 10.3 % / CC1/2: 1 / Net I/σ(I): 14.7 |
反射 シェル | 解像度: 1.43→1.58 Å / Num. unique obs: 2156 / CC1/2: 0.67 |
-解析
ソフトウェア |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
精密化 | 構造決定の手法: 分子置換 開始モデル: 8A27 解像度: 1.43→57.31 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.952 / SU B: 3.066 / SU ML: 0.058 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R: 0.094 / ESU R Free: 0.096 / 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 : WITH TLS ADDED
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 100.11 Å2 / Biso mean: 30.325 Å2 / Biso min: 12.2 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 1.43→57.31 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
拘束条件 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS精密化 シェル | 解像度: 1.43→1.467 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化 TLS | 手法: refined / Origin x: 4.0271 Å / Origin y: -8.7772 Å / Origin z: -14.3764 Å
|