+Open data
-Basic information
Entry | Database: PDB / ID: 6vgl | ||||||
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Title | JAK2 JH1 in complex with ruxolitinib | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Janus associated kinase / JAK2 / kinase domain / JH1 / kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information interleukin-35-mediated signaling pathway / 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 / granulocyte macrophage colony-stimulating factor receptor complex ...interleukin-35-mediated signaling pathway / 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 / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / Signaling by Erythropoietin / 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 / positive regulation of platelet activation / positive regulation of MHC class II biosynthetic process / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / regulation of nitric oxide biosynthetic process / acetylcholine receptor binding / interleukin-12-mediated signaling pathway / interleukin-3-mediated signaling pathway / 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 / response to hydroperoxide / positive regulation of cell-substrate adhesion / negative regulation of cardiac muscle cell apoptotic process / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / 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 / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / 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 / actin filament polymerization / extrinsic component of cytoplasmic side of plasma membrane / 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 / caveola / endosome lumen / positive regulation of cell differentiation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Model details | Co-crystal structure of JAK2 JH1 and ruxolitinib complex | ||||||
Authors | Davis, R.R. / Schonbrunn, E. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof. Authors: 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6vgl.cif.gz | 273.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6vgl.ent.gz | 219.4 KB | Display | PDB format |
PDBx/mmJSON format | 6vgl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vg/6vgl ftp://data.pdbj.org/pub/pdb/validation_reports/vg/6vgl | HTTPS FTP |
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-Related structure data
Related structure data | 6vn8C 6vnbC 6vncC 6vneC 6vnfC 6vngC 6vnhC 6vniC 6vnjC 6vnkC 6vnlC 6vnmC 6vs3C 6vsnC 2xa4S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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3 |
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4 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: GLN / Beg label comp-ID: GLN / End auth comp-ID: ALA / End label comp-ID: ALA / Auth seq-ID: 843 - 1131 / Label seq-ID: 19 - 307
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-Components
#1: Protein | Mass: 36455.441 Da / Num. of mol.: 4 / Fragment: JAK2 kinase domain (UNP residues 840-1132) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Plasmid: pcDNA 3.3 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) References: UniProt: O60674, non-specific protein-tyrosine kinase #2: Chemical | ChemComp-RXT / ( #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.05 Å3/Da / Density % sol: 59.72 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 5.5 Details: 0.1 M Bis-Tris, pH 5.5, 0.2 M sodium chloride, 25% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 4, 2019 |
Radiation | Monochromator: Rosenbaum-Rock double crystal Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→52.815 Å / Num. obs: 138102 / % possible obs: 99.6 % / Redundancy: 3.73 % / Biso Wilson estimate: 36.3 Å2 / CC1/2: 1 / Rrim(I) all: 0.078 / Net I/σ(I): 11.9 |
Reflection shell | Resolution: 1.9→1.95 Å / Mean I/σ(I) obs: 0.8 / Num. unique obs: 10192 / CC1/2: 0.34 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 2XA4 Resolution: 1.9→52.815 Å / SU ML: 0.28 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 24.61
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 128.77 Å2 / Biso mean: 44.5967 Å2 / Biso min: 22.02 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.9→52.815 Å
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Refine LS restraints NCS |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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