+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6g9m | ||||||
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タイトル | Fragment-based discovery of a highly potent, orally bioavailable inhibitor which modulates the phosphorylation and catalytic activity of ERK1/2 | ||||||
要素 | Mitogen-activated protein kinase 1 | ||||||
キーワード | SIGNALING PROTEIN / Erk2 Kinase inhibitor | ||||||
機能・相同性 | 機能・相同性情報 phospho-PLA2 pathway / Signaling by MAPK mutants / RAF-independent MAPK1/3 activation / Suppression of apoptosis / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / ERKs are inactivated ...phospho-PLA2 pathway / Signaling by MAPK mutants / RAF-independent MAPK1/3 activation / Suppression of apoptosis / Signaling by Activin / Gastrin-CREB signalling pathway via PKC and MAPK / cardiac neural crest cell development involved in heart development / caveolin-mediated endocytosis / cytosine metabolic process / ERKs are inactivated / response to epidermal growth factor / Signaling by MAP2K mutants / Signaling by NODAL / RSK activation / Golgi Cisternae Pericentriolar Stack Reorganization / regulation of cellular pH / positive regulation of macrophage proliferation / outer ear morphogenesis / Regulation of the apoptosome activity / regulation of Golgi inheritance / ERBB signaling pathway / labyrinthine layer blood vessel development / mammary gland epithelial cell proliferation / trachea formation / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / regulation of stress-activated MAPK cascade / IFNG signaling activates MAPKs / Frs2-mediated activation / positive regulation of macrophage chemotaxis / lung morphogenesis / ERBB2-ERBB3 signaling pathway / response to exogenous dsRNA / regulation of cytoskeleton organization / Activation of the AP-1 family of transcription factors / face development / ERK/MAPK targets / androgen receptor signaling pathway / 仮足 / RUNX2 regulates osteoblast differentiation / Recycling pathway of L1 / progesterone receptor signaling pathway / MAPK1 (ERK2) activation / negative regulation of cell differentiation / Bergmann glial cell differentiation / positive regulation of telomere capping / thyroid gland development / Advanced glycosylation endproduct receptor signaling / steroid hormone mediated signaling pathway / RHO GTPases Activate NADPH Oxidases / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Regulation of HSF1-mediated heat shock response / MAP kinase activity / regulation of ossification / RHO GTPases Activate WASPs and WAVEs / 分裂促進因子活性化タンパク質キナーゼ / phosphatase binding / Nuclear events stimulated by ALK signaling in cancer / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / Schwann cell development / stress-activated MAPK cascade / Growth hormone receptor signaling / lipopolysaccharide-mediated signaling pathway / positive regulation of telomerase activity / cellular response to cadmium ion / positive regulation of telomere maintenance via telomerase / ERK1 and ERK2 cascade / NPAS4 regulates expression of target genes / cellular response to amino acid starvation / 髄鞘 / NCAM signaling for neurite out-growth / phosphotyrosine residue binding / RNA polymerase II CTD heptapeptide repeat kinase activity / ESR-mediated signaling / insulin-like growth factor receptor signaling pathway / thymus development / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription / Signal transduction by L1 / カベオラ / long-term synaptic potentiation / Negative regulation of FGFR3 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / FCERI mediated MAPK activation / Negative regulation of FGFR2 signaling / FCGR3A-mediated phagocytosis / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / B cell receptor signaling pathway / peptidyl-threonine phosphorylation / Spry regulation of FGF signaling / response to nicotine / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / regulation of protein stability / Oncogene Induced Senescence / 紡錘体 / Regulation of actin dynamics for phagocytic cup formation 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / フーリエ合成 / 解像度: 1.86 Å | ||||||
データ登録者 | O'Reilly, M. | ||||||
引用 | ジャーナル: J. Med. Chem. / 年: 2018 タイトル: Fragment-Based Discovery of a Potent, Orally Bioavailable Inhibitor That Modulates the Phosphorylation and Catalytic Activity of ERK1/2. 著者: Heightman, T.D. / Berdini, V. / Braithwaite, H. / Buck, I.M. / Cassidy, M. / Castro, J. / Courtin, A. / Day, J.E.H. / East, C. / Fazal, L. / Graham, B. / Griffiths-Jones, C.M. / Lyons, J.F. / ...著者: Heightman, T.D. / Berdini, V. / Braithwaite, H. / Buck, I.M. / Cassidy, M. / Castro, J. / Courtin, A. / Day, J.E.H. / East, C. / Fazal, L. / Graham, B. / Griffiths-Jones, C.M. / Lyons, J.F. / Martins, V. / Muench, S. / Munck, J.M. / Norton, D. / O'Reilly, M. / Palmer, N. / Pathuri, P. / Reader, M. / Rees, D.C. / Rich, S.J. / Richardson, C. / Saini, H. / Thompson, N.T. / Wallis, N.G. / Walton, H. / Wilsher, N.E. / Woolford, A.J. / Cooke, M. / Cousin, D. / Onions, S. / Shannon, J. / Watts, J. / Murray, C.W. | ||||||
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 | 6g9m.cif.gz | 166.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6g9m.ent.gz | 134.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6g9m.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/g9/6g9m ftp://data.pdbj.org/pub/pdb/validation_reports/g9/6g9m | HTTPS FTP |
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-関連構造データ
-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: 42551.922 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: MAPK1, ERK2, PRKM1, PRKM2 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) 参照: UniProt: P28482, 分裂促進因子活性化タンパク質キナーゼ | ||||
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#2: 化合物 | #3: 化合物 | ChemComp-ESW / | #4: 水 | ChemComp-HOH / | |
-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: 2.31 Å3/Da / 溶媒含有率: 46.76 % |
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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: 7.2 詳細: 2M (NH4)2SO4 32% MPEG 2000 .02M Mercaptoethanol .1M pH=7.2 HEPES/NaOH |
-データ収集
回折 | 平均測定温度: 100 K |
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放射光源 | 由来: 回転陽極 / タイプ: RIGAKU FR-X / 波長: 1.54178 Å |
検出器 | タイプ: DECTRIS PILATUS 300K / 検出器: PIXEL / 日付: 2015年4月16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: 1.54178 Å / 相対比: 1 |
反射 | 解像度: 1.86→30.06 Å / Num. obs: 31764 / % possible obs: 97.3 % / 冗長度: 2.8 % / Biso Wilson estimate: 26.89 Å2 / Rrim(I) all: 0.049 / Net I/σ(I): 15.1 |
反射 シェル | 解像度: 1.86→1.87 Å / Mean I/σ(I) obs: 1.3 / Num. unique obs: 436 / Rrim(I) all: 0.794 / % possible all: 89.7 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: フーリエ合成 / 解像度: 1.86→28.92 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.934 / SU R Cruickshank DPI: 0.203 / 交差検証法: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.14 / SU Rfree Blow DPI: 0.132 / SU Rfree Cruickshank DPI: 0.125
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原子変位パラメータ | Biso mean: 36.971 Å2
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Refine analyze | Luzzati coordinate error obs: 0.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 解像度: 1.86→28.92 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 1.86→1.92 Å / Total num. of bins used: 16
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精密化 TLS | 手法: refined / Origin x: -1.5115 Å / Origin y: 3.6013 Å / Origin z: 38.0279 Å
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精密化 TLSグループ | Selection details: { A|11 - A|356 } |