+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 4c62 | ||||||
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タイトル | Inhibitors of Jak2 Kinase domain | ||||||
要素 | TYROSINE-PROTEIN KINASE JAK2 | ||||||
キーワード | TRANSFERASE (転移酵素) | ||||||
機能・相同性 | 機能・相同性情報 interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / Signaling by Erythropoietin ...interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / Signaling by Erythropoietin / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / interleukin-12 receptor binding / post-embryonic hemopoiesis / collagen-activated signaling pathway / Erythropoietin activates STAT5 / Erythropoietin activates Phospholipase C gamma (PLCG) / interleukin-5-mediated signaling pathway / response to interleukin-12 / positive regulation of leukocyte proliferation / interleukin-12 receptor complex / activation of Janus kinase activity / interleukin-23 receptor complex / positive regulation of platelet aggregation / tyrosine phosphorylation of STAT protein / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / positive regulation of platelet activation / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / interleukin-3-mediated signaling pathway / regulation of nitric oxide biosynthetic process / acetylcholine receptor binding / cellular response to interleukin-3 / Signaling by Leptin / Interleukin-12 signaling / positive regulation of signaling receptor activity / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / positive regulation of cell-substrate adhesion / response to hydroperoxide / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / negative regulation of cardiac muscle cell apoptotic process / positive regulation of epithelial cell apoptotic process / axon regeneration / growth hormone receptor signaling pathway / peptide hormone receptor binding / intrinsic apoptotic signaling pathway in response to oxidative stress / IFNG signaling activates MAPKs / extrinsic component of plasma membrane / Interleukin-20 family signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin-6 signaling / enzyme-linked receptor protein signaling pathway / interleukin-6-mediated signaling pathway / negative regulation of cell-cell adhesion / Prolactin receptor signaling / positive regulation of interleukin-17 production / negative regulation of DNA binding / MAPK3 (ERK1) activation / response to amine / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / mesoderm development / positive regulation of natural killer cell proliferation / positive regulation of SMAD protein signal transduction / cell surface receptor signaling pathway via JAK-STAT / platelet-derived growth factor receptor signaling pathway / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / growth hormone receptor signaling pathway via JAK-STAT / response to tumor necrosis factor / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / Erythropoietin activates RAS / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / positive regulation of apoptotic signaling pathway / Signaling by CSF3 (G-CSF) / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of T cell proliferation / tumor necrosis factor-mediated signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / post-translational protein modification / 赤血球形成 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / カベオラ / endosome lumen / positive regulation of cell differentiation 類似検索 - 分子機能 | ||||||
生物種 | HOMO SAPIENS (ヒト) | ||||||
手法 | X線回折 / 分子置換 / 解像度: 2.75 Å | ||||||
データ登録者 | Read, J. / Green, I. / Pollard, H. / Howard, T. | ||||||
引用 | ジャーナル: J.Med.Chem. / 年: 2014 タイトル: Discovery of 1-Methyl-1H-Imidazole Derivatives as Potent Jak2 Inhibitors. 著者: Su, Q. / Ioannidis, S. / Chuaqui, C. / Almeida, L. / Alimzhanov, M. / Bebernitz, G. / Bell, K. / Block, M. / Howard, T. / Huang, S. / Huszar, D. / Read, J.A. / Rivard Costa, C. / Shi, J. / ...著者: Su, Q. / Ioannidis, S. / Chuaqui, C. / Almeida, L. / Alimzhanov, M. / Bebernitz, G. / Bell, K. / Block, M. / Howard, T. / Huang, S. / Huszar, D. / Read, J.A. / Rivard Costa, C. / Shi, J. / Su, M. / Ye, M. / Zinda, M. #1: ジャーナル: J.Med.Chem. / 年: 2011 タイトル: Discovery of 5-Chloro-N2-[(1S)-1-(5-Fluoropyrimidin-2-Yl)Ethyl]-N4-(5-Methyl-1H-Pyrazol-3-Yl)Pyrimidine-2,4-Diamine (Azd1480) as a Novel Inhibitor of the Jak/Stat Pathway. 著者: Ioannidis, S. / Lamb, M.L. / Wang, T. / Almeida, L. / Block, M.H. / Davies, A.M. / Peng, B. / Su, M. / Zhang, H. / Hoffmann, E. / Rivard, C. / Green, I. / Howard, T. / Pollard, H. / Read, J. ...著者: Ioannidis, S. / Lamb, M.L. / Wang, T. / Almeida, L. / Block, M.H. / Davies, A.M. / Peng, B. / Su, M. / Zhang, H. / Hoffmann, E. / Rivard, C. / Green, I. / Howard, T. / Pollard, H. / Read, J. / Alimzhanov, M. / Bebernitz, G. / Bell, K. / Ye, M. / Huszar, D. / Zinda, M. | ||||||
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 | 4c62.cif.gz | 240.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb4c62.ent.gz | 193.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 4c62.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/c6/4c62 ftp://data.pdbj.org/pub/pdb/validation_reports/c6/4c62 | 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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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: (詳細: A) NCS oper:
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-要素
#1: タンパク質 | 分子量: 35095.816 Da / 分子数: 2 / 断片: KINASE DOMAIN RESIDUES 835-1132 / 変異: YES / 由来タイプ: 組換発現 / 由来: (組換発現) HOMO SAPIENS (ヒト) / 発現宿主: ESCHERICHIA COLI (大腸菌) / 株 (発現宿主): BL21 / Variant (発現宿主): STAR 参照: UniProt: O60674, EC: 2.7.1.112, non-specific protein-tyrosine kinase #2: 化合物 | #3: 化合物 | #4: 水 | ChemComp-HOH / | 配列の詳細 | K943 AND K945A DOUBLE MUTANT | |
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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: 2.82 Å3/Da / 溶媒含有率: 56.4 % / 解説: NONE |
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結晶化 | pH: 7 / 詳細: pH 7 |
-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 MICROMAX-007 / 波長: 1.5418 |
検出器 | タイプ: MARRESEARCH / 検出器: IMAGE PLATE / 日付: 2008年6月18日 / 詳細: MIRRORS |
放射 | モノクロメーター: NI FILTER / 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: 1.5418 Å / 相対比: 1 |
反射 | 解像度: 2.75→21.2 Å / Num. obs: 19353 / % possible obs: 99.4 % / Observed criterion σ(I): 2 / 冗長度: 4 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 11.6 |
反射 シェル | 解像度: 2.75→2.9 Å / 冗長度: 3.7 % / Rmerge(I) obs: 0.5 / Mean I/σ(I) obs: 2.1 / % possible all: 98.7 |
-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: PDB ENTRY 2XA4 解像度: 2.75→21 Å / Cor.coef. Fo:Fc: 0.937 / Cor.coef. Fo:Fc free: 0.903 / SU B: 25.38 / SU ML: 0.259 / 交差検証法: THROUGHOUT / ESU R Free: 0.345 / 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
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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 mean: 50.193 Å2
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精密化ステップ | サイクル: LAST / 解像度: 2.75→21 Å
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拘束条件 |
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