+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ba4 | ||||||
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タイトル | Crystal structure of JAK2 JH2-V617F in complex with Bemcentinib | ||||||
要素 | Tyrosine-protein kinase JAK2 | ||||||
キーワード | TRANSFERASE / Janus kinase / pseudokinase / inhibitor complex / JAK2 / JH2 | ||||||
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 / erythropoietin-mediated signaling pathway ...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 / erythropoietin-mediated signaling pathway / interleukin-23-mediated 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 platelet aggregation / positive regulation of MHC class II biosynthetic process / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / acetylcholine receptor binding / interleukin-12-mediated signaling pathway / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-3-mediated signaling pathway / cellular response to interleukin-3 / regulation of nitric oxide biosynthetic process / Signaling by Leptin / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of signaling receptor activity / positive regulation of epithelial cell apoptotic process / 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 / response to hydroperoxide / axon regeneration / growth hormone receptor signaling pathway / negative regulation of cardiac muscle cell apoptotic process / intrinsic apoptotic signaling pathway in response to oxidative stress / peptide hormone receptor binding / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / Interleukin-20 family signaling / negative regulation of cell-cell adhesion / Interleukin-6 signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / interleukin-6-mediated signaling pathway / enzyme-linked receptor protein signaling pathway / Prolactin receptor signaling / MAPK3 (ERK1) activation / negative regulation of DNA binding / positive regulation of interleukin-17 production / positive regulation of nitric-oxide synthase biosynthetic process / response to amine / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / 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 / response to tumor necrosis factor / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / Erythropoietin activates RAS / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / Signaling by CSF3 (G-CSF) / tumor necrosis factor-mediated signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / post-translational protein modification / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / 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: 2.1 Å | ||||||
データ登録者 | Haikarainen, T. / Silvennoinen, O. | ||||||
資金援助 | フィンランド, 1件
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引用 | ジャーナル: Pharmaceuticals / 年: 2023 タイトル: Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain. 著者: Virtanen, A.T. / Haikarainen, T. / Sampathkumar, P. / Palmroth, M. / Liukkonen, S. / Liu, J. / Nekhotiaeva, N. / Hubbard, S.R. / Silvennoinen, O. | ||||||
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 | 8ba4.cif.gz | 266.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8ba4.ent.gz | 173.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8ba4.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 | 8ba4_validation.pdf.gz | 688.8 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8ba4_full_validation.pdf.gz | 693.2 KB | 表示 | |
XML形式データ | 8ba4_validation.xml.gz | 23.1 KB | 表示 | |
CIF形式データ | 8ba4_validation.cif.gz | 32.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ba/8ba4 ftp://data.pdbj.org/pub/pdb/validation_reports/ba/8ba4 | HTTPS FTP |
-関連構造データ
関連構造データ | 8b8nC 8b8uC 8b99C 8b9eC 8b9hC 8ba2C 8ba3C 8babC 8bakC 8ex0C 8ex1C 8ex2C 4fvrS 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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2 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 33169.004 Da / 分子数: 2 / 変異: W659A, W777A, F794H, V617F / 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 | ChemComp-Q8U / | #3: 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: 2.29 Å3/Da / 溶媒含有率: 46.2 % |
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結晶化 | 温度: 277 K / 手法: 蒸気拡散法, ハンギングドロップ法 / pH: 8 / 詳細: 0.1M Tris pH 8, 20% PEG4000, 0.2M Na-acetate |
-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: 0.97625 Å |
検出器 | タイプ: DECTRIS EIGER2 XE 16M / 検出器: PIXEL / 日付: 2020年11月24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: 0.97625 Å / 相対比: 1 |
反射 | 解像度: 2.1→53.021 Å / Num. obs: 65757 / % possible obs: 95.3 % / 冗長度: 1.8 % / Biso Wilson estimate: 33.84 Å2 / CC1/2: 0.995 / Net I/σ(I): 6.62 |
反射 シェル | 解像度: 2.1→2.23 Å / 冗長度: 1.9 % / Mean I/σ(I) obs: 1.13 / Num. unique obs: 10618 / CC1/2: 0.461 / % possible all: 95.2 |
-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: 4fvr 解像度: 2.1→50.02 Å / SU ML: 0.3214 / 交差検証法: FREE R-VALUE / σ(F): 1.29 / 位相誤差: 29.9017 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2
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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 / 溶媒モデル: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 44.49 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.1→50.02 Å
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拘束条件 |
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LS精密化 シェル |
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