+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8g8o | ||||||
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タイトル | The crystal structure of JAK2 in complex with Compound 31 | ||||||
要素 | Tyrosine-protein kinase JAK2 | ||||||
キーワード | TRANSFERASE/Inhibitor / inhibitor / JAK2 / kinase / TRANSFERASE / TRANSFERASE-Inhibitor complex | ||||||
機能・相同性 | 機能・相同性情報 interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid 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 / granulocyte macrophage colony-stimulating factor receptor complex ...interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid 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 / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / Signaling by Erythropoietin / collagen-activated signaling pathway / interleukin-12 receptor binding / Erythropoietin activates STAT5 / interleukin-5-mediated signaling pathway / response to interleukin-12 / Erythropoietin activates Phospholipase C gamma (PLCG) / positive regulation of leukocyte proliferation / post-embryonic hemopoiesis / interleukin-12 receptor complex / activation of Janus kinase activity / tyrosine phosphorylation of STAT protein / interleukin-23 receptor complex / positive regulation of MHC class II biosynthetic process / positive regulation of platelet aggregation / Interleukin-23 signaling / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / acetylcholine receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / Signaling by Leptin / regulation of nitric oxide biosynthetic process / positive regulation of signaling receptor activity / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of epithelial cell apoptotic process / response to hydroperoxide / positive regulation of natural killer cell proliferation / positive regulation of cell-substrate adhesion / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / axon regeneration / growth hormone receptor signaling pathway / peptide hormone receptor binding / negative regulation of cardiac muscle cell apoptotic process / intrinsic apoptotic signaling pathway in response to oxidative stress / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / Interleukin-20 family signaling / interleukin-6-mediated signaling pathway / negative regulation of cell-cell adhesion / Interleukin-6 signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / enzyme-linked receptor protein signaling pathway / Prolactin receptor signaling / MAPK3 (ERK1) activation / response to amine / positive regulation of interleukin-17 production / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / mesoderm development / cell surface receptor signaling pathway via JAK-STAT / positive regulation of SMAD protein signal transduction / 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 / Regulation of IFNG signaling / type II interferon-mediated signaling pathway / Erythropoietin activates RAS / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / positive regulation of T cell proliferation / Signaling by CSF3 (G-CSF) / positive regulation of tyrosine phosphorylation of STAT protein / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of vascular associated smooth muscle cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / erythrocyte differentiation / post-translational protein modification / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / caveola / endosome lumen / positive regulation of cell differentiation / positive regulation of apoptotic signaling pathway 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: 2.2 Å | ||||||
データ登録者 | Miller, S.T. / Ellis, D.A. | ||||||
資金援助 | 1件
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引用 | ジャーナル: J.Med.Chem. / 年: 2023 タイトル: Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase ...タイトル: Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase Activity, While Driving Potency and Aqueous Solubility. 著者: Gordhan, H.M. / Miller, S.T. / Clancy, D.C. / Ina, M. / McDougal, A.V. / Cutno, D.K. / Brown, R.V. / Lichorowic, C.L. / Sturdivant, J.M. / Vick, K.A. / Williams, S.S. / deLong, M.A. / White, ...著者: Gordhan, H.M. / Miller, S.T. / Clancy, D.C. / Ina, M. / McDougal, A.V. / Cutno, D.K. / Brown, R.V. / Lichorowic, C.L. / Sturdivant, J.M. / Vick, K.A. / Williams, S.S. / deLong, M.A. / White, J.C. / Kopczynski, C.C. / Ellis, D.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 | 8g8o.cif.gz | 135.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8g8o.ent.gz | 102.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8g8o.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 | 8g8o_validation.pdf.gz | 1006 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8g8o_full_validation.pdf.gz | 1010.1 KB | 表示 | |
XML形式データ | 8g8o_validation.xml.gz | 23 KB | 表示 | |
CIF形式データ | 8g8o_validation.cif.gz | 31.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/g8/8g8o ftp://data.pdbj.org/pub/pdb/validation_reports/g8/8g8o | HTTPS FTP |
-関連構造データ
関連構造データ | 8g6zC 8g8xC 3iokS 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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単位格子 |
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-要素
#1: タンパク質 | 分子量: 37458.535 Da / 分子数: 2 / 変異: M1073S, F1076T / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: JAK2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: O60674, non-specific protein-tyrosine kinase #2: 化合物 | #3: 化合物 | ChemComp-DMS / | #4: 化合物 | ChemComp-EDO / | #5: 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: 42.54 % |
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結晶化 | 温度: 293 K / 手法: 蒸気拡散法, ハンギングドロップ法 / 詳細: PEG 3350, ammonium acetate, HEPES |
-データ収集
回折 | 平均測定温度: 100 K / 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: I03 / 波長: 0.9763 Å |
検出器 | タイプ: DECTRIS EIGER2 X 16M / 検出器: PIXEL / 日付: 2021年6月27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: 0.9763 Å / 相対比: 1 |
反射 | 解像度: 2.2→47.18 Å / Num. obs: 31923 / % possible obs: 99.9 % / 冗長度: 6.5 % / Rmerge(I) obs: 0.175 / Rpim(I) all: 0.075 / Net I/σ(I): 8.2 |
反射 シェル | 解像度: 2.2→2.27 Å / Rmerge(I) obs: 1.319 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 2810 / Rpim(I) all: 0.534 |
-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: 3IOK 解像度: 2.2→47.18 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.921 / SU B: 4.22 / SU ML: 0.116 / 交差検証法: THROUGHOUT / ESU R: 0.058 / ESU R Free: 0.044 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD / 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 38.111 Å2
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精密化ステップ | サイクル: 1 / 解像度: 2.2→47.18 Å
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拘束条件 |
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