+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6vnk | ||||||
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タイトル | JAK2 JH1 in complex with PN4-073 | ||||||
要素 | Tyrosine-protein kinase JAK2 | ||||||
キーワード | TRANSFERASE (転移酵素) / janus associated kinase / JAK2 / kinase domain (キナーゼ) / JH1 / kinase (キナーゼ) | ||||||
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 / activation of Janus kinase activity / interleukin-12 receptor complex / 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 / positive regulation of signaling receptor activity / Interleukin-12 signaling / 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 / peptide hormone receptor binding / growth hormone receptor signaling pathway / 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 / positive regulation of natural killer cell proliferation / mesoderm development / 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 / positive regulation of apoptotic signaling pathway / extrinsic 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 / actin filament polymerization / extrinsic component of cytoplasmic side of plasma membrane / 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 / シンクロトロン / 分子置換 / 解像度: 2 Å | ||||||
Model details | Co-crystal structure of JAK2 JH1 and ruxolitinib complex | ||||||
データ登録者 | Davis, R.R. / Schonbrunn, E. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: J.Med.Chem. / 年: 2021 タイトル: Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof. 著者: Davis, R.R. / Li, B. / Yun, S.Y. / Chan, A. / Nareddy, P. / Gunawan, S. / Ayaz, M. / Lawrence, H.R. / Reuther, G.W. / Lawrence, N.J. / Schonbrunn, E. | ||||||
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 | 6vnk.cif.gz | 263.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6vnk.ent.gz | 211.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6vnk.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/vn/6vnk ftp://data.pdbj.org/pub/pdb/validation_reports/vn/6vnk | HTTPS FTP |
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-関連構造データ
関連構造データ | 6vglC 6vn8C 6vnbC 6vncC 6vneC 6vnfC 6vngC 6vnhC 6vniC 6vnjC 6vnlC 6vnmC 6vs3C 6vsnC 2xa4S 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 |
-リンク
-集合体
登録構造単位 |
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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:
NCSドメイン領域: Ens-ID: 1
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-要素
#1: タンパク質 | 分子量: 36455.441 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: JAK2 / プラスミド: pcDNA 3.3 / 発現宿主: Homo sapiens (ヒト) / 株 (発現宿主): Expi293F 参照: UniProt: O60674, non-specific protein-tyrosine kinase #2: 化合物 | ChemComp-RXT / ( #3: 水 | ChemComp-HOH / | 研究の焦点であるリガンドがあるか | Y | 非ポリマーの詳細 | PN4-073 is a racemic mixture of R-form and S-form of ruxolitinib. The protein selects for the R- ...PN4-073 is a racemic mixture of R-form and S-form of ruxolitinib. The protein selects for the R-form which is RXT | |
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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: 3.04 Å3/Da / 溶媒含有率: 59.56 % |
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結晶化 | 温度: 291 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 5.5 / 詳細: 0.1 M Bis-Tris pH 5.5, 0.2 M NaCl, 25% PEG 3350 |
-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: APS / ビームライン: 23-ID-B / 波長: 1.0332 Å |
検出器 | タイプ: DECTRIS PILATUS3 6M / 検出器: PIXEL / 日付: 2019年10月16日 |
放射 | モノクロメーター: ROSENBAUM-ROCK DOUBLE-CRYSTAL si(220) 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: 1.0332 Å / 相対比: 1 |
反射 | 解像度: 2→40.907 Å / Num. obs: 199608 / % possible obs: 93.3 % / 冗長度: 2.8 % / CC1/2: 1 / Rrim(I) all: 0.115 / Net I/σ(I): 9.9 |
反射 シェル | 解像度: 2→2.07 Å / Num. unique obs: 11191 / CC1/2: 0.41 / % possible all: 94.8 |
-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: 2XA4 解像度: 2→40.907 Å / SU ML: 0.38 / 交差検証法: THROUGHOUT / σ(F): 1.33 / 位相誤差: 32.53
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 128.28 Å2 / Biso mean: 51.6178 Å2 / Biso min: 25.85 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 2→40.907 Å
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Refine LS restraints NCS |
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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