+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 1ouk | ||||||
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タイトル | The structure of p38 alpha in complex with a pyridinylimidazole inhibitor | ||||||
要素 | Mitogen-activated protein kinase 14MAPK14 | ||||||
キーワード | TRANSFERASE (転移酵素) / MAP kinase (分裂促進因子活性化タンパク質キナーゼ) / hydrophobic pocket / Kinase domain (キナーゼ) / ATP binding domain | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions / cartilage condensation ...positive regulation of cyclase activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions / cartilage condensation / cellular response to UV-B / Platelet sensitization by LDL / stress-activated protein kinase signaling cascade / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / positive regulation of muscle cell differentiation / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / response to dietary excess / Activation of the AP-1 family of transcription factors / ERK/MAPK targets / regulation of cytokine production involved in inflammatory response / p38MAPK cascade / Β酸化 / cellular response to lipoteichoic acid / MAP kinase kinase activity / response to muramyl dipeptide / RHO GTPases Activate NADPH Oxidases / regulation of ossification / MAP kinase activity / 分裂促進因子活性化タンパク質キナーゼ / cellular response to vascular endothelial growth factor stimulus / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / signal transduction in response to DNA damage / lipopolysaccharide-mediated signaling pathway / negative regulation of inflammatory response to antigenic stimulus / positive regulation of cardiac muscle cell proliferation / p38MAPK events / striated muscle cell differentiation / response to muscle stretch / positive regulation of brown fat cell differentiation / positive regulation of interleukin-12 production / osteoclast differentiation / positive regulation of erythrocyte differentiation / placenta development / DNA damage checkpoint signaling / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / 細胞分化 / positive regulation of glucose import / negative regulation of canonical Wnt signaling pathway / response to insulin / NOD1/2 Signaling Pathway / 骨 / cell morphogenesis / 凝固・線溶系 / osteoblast differentiation / cellular response to virus / VEGFA-VEGFR2 Pathway / 紡錘体 / positive regulation of protein import into nucleus / ADP signalling through P2Y purinoceptor 1 / glucose metabolic process / positive regulation of reactive oxygen species metabolic process / 走化性 / 細胞老化 / cellular response to tumor necrosis factor / protein phosphatase binding / peptidyl-serine phosphorylation / 血管新生 / Oxidative Stress Induced Senescence / secretory granule lumen / cellular response to lipopolysaccharide / Regulation of TP53 Activity through Phosphorylation / ficolin-1-rich granule lumen / transcription by RNA polymerase II / cell surface receptor signaling pathway / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / enzyme binding / シグナル伝達 / positive regulation of transcription by RNA polymerase II / ミトコンドリア / extracellular region / 核質 / ATP binding 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 / フーリエ合成 / 解像度: 2.5 Å | ||||||
データ登録者 | Fitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G. | ||||||
引用 | ジャーナル: Nat.Struct.Biol. / 年: 2003 タイトル: Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity 著者: Fitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G. #1: ジャーナル: J.Med.Chem. / 年: 1999 タイトル: Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase 著者: Liverton, N.J. / Butcher, J.W. / Claiborne, C.F. / Claremon, D.A. / Libby, B.E. / Nguyen, K.T. / Pitzenberger, S.M. / Selnick, H.G. / Smith, G.R. / Tebben, A. / Vacca, J.P. / Varga, S.L. / ...著者: Liverton, N.J. / Butcher, J.W. / Claiborne, C.F. / Claremon, D.A. / Libby, B.E. / Nguyen, K.T. / Pitzenberger, S.M. / Selnick, H.G. / Smith, G.R. / Tebben, A. / Vacca, J.P. / Varga, S.L. / Agarwal, L. / Dancheck, K. / Forsyth, A.J. / Fletcher, D.S. / Frantz, B. / Hanlon, W.A. / Harper, C.F. / Hofsess, S.J. / Kostura, M. / Lin, J. / Luell, S. / O'Neill, E.A. / O'Keefe, S.J. | ||||||
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 | 1ouk.cif.gz | 87.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb1ouk.ent.gz | 64.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 1ouk.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/ou/1ouk ftp://data.pdbj.org/pub/pdb/validation_reports/ou/1ouk | 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: 41998.938 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: MAPK14 / プラスミド: pET / 生物種 (発現宿主): Escherichia coli / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 株 (発現宿主): BL21(DE3) / 参照: UniProt: Q16539, EC: 2.7.1.37 |
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#2: 化合物 | ChemComp-SO4 / |
#3: 化合物 | ChemComp-084 / |
#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: 3.02 Å3/Da / 溶媒含有率: 59.24 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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結晶化 | 温度: 298 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 7 詳細: Sodium citrate, Ammunium sulfate, HEPES buffer, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
結晶化 | *PLUS pH: 7.5 / 手法: 蒸気拡散法 / 詳細: Wilson, K.P., (1996) J.Biol.Chem., 271, 27696. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
溶液の組成 | *PLUS
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-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: シンクロトロン / サイト: APS / ビームライン: 17-ID / 波長: 1 Å |
検出器 | タイプ: MARRESEARCH / 検出器: CCD / 日付: 2000年6月8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 Å / 相対比: 1 |
反射 | 解像度: 2.5→35 Å / Num. all: 18302 / Num. obs: 18247 / % possible obs: 99.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / 冗長度: 5.8 % / Biso Wilson estimate: 42.2 Å2 / Rsym value: 0.102 / Net I/σ(I): 8 |
反射 シェル | 解像度: 2.5→2.6 Å / 冗長度: 5.7 % / Mean I/σ(I) obs: 1.6 / Num. unique all: 2982 / Rsym value: 0.378 / % possible all: 99.7 |
反射 | *PLUS Rmerge(I) obs: 0.102 |
反射 シェル | *PLUS % possible obs: 99.7 % / Num. unique obs: 2982 / Rmerge(I) obs: 0.378 |
-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 開始モデル: 1WFC 解像度: 2.5→30 Å / Isotropic thermal model: Anisotropic / 交差検証法: THROUGHOUT / σ(F): 0 / σ(I): 0 / 立体化学のターゲット値: Engh & Huber / 詳細: As implemented in CNX
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溶媒の処理 | 溶媒モデル: MASK / Bsol: 34.34 Å2 / ksol: 0.314 e/Å3 | |||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 41.6 Å2
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Refine analyze |
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精密化ステップ | サイクル: LAST / 解像度: 2.5→30 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.5→2.6 Å
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精密化 | *PLUS 最低解像度: 30 Å | |||||||||||||||||||||||||
溶媒の処理 | *PLUS | |||||||||||||||||||||||||
原子変位パラメータ | *PLUS | |||||||||||||||||||||||||
拘束条件 | *PLUS
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