+Open data
-Basic information
Entry | Database: PDB / ID: 6x8e | ||||||
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Title | Crystal structure of JAK2 with Compound 11 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE / kinase | ||||||
Function / homology | Function and homology information 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 / interleukin-12 receptor binding / Signaling by Erythropoietin / collagen-activated signaling pathway / 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 / interleukin-23 receptor complex / tyrosine phosphorylation of STAT protein / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / positive regulation of platelet aggregation / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of platelet activation / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / acetylcholine receptor binding / 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-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / positive regulation of epithelial cell apoptotic process / positive regulation of natural killer cell proliferation / response to hydroperoxide / 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 / IFNG signaling activates MAPKs / extrinsic component of plasma membrane / 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 / positive regulation of interleukin-17 production / response to amine / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / mesoderm development / 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 / positive regulation of T cell proliferation / extrinsic apoptotic signaling pathway / 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 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å | ||||||
Authors | Vajdos, F.F. / Knafels, J.D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. Authors: Gerstenberger, B.S. / Ambler, C. / Arnold, E.P. / Banker, M.E. / Brown, M.F. / Clark, J.D. / Dermenci, A. / Dowty, M.E. / Fensome, A. / Fish, S. / Hayward, M.M. / Hegen, M. / Hollingshead, B. ...Authors: Gerstenberger, B.S. / Ambler, C. / Arnold, E.P. / Banker, M.E. / Brown, M.F. / Clark, J.D. / Dermenci, A. / Dowty, M.E. / Fensome, A. / Fish, S. / Hayward, M.M. / Hegen, M. / Hollingshead, B.D. / Knafels, J.D. / Lin, D.W. / Lin, T.H. / Owen, D.R. / Saiah, E. / Sharma, R. / Vajdos, F.F. / Xing, L. / Yang, X. / Yang, X. / Wright, S.W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6x8e.cif.gz | 145.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6x8e.ent.gz | 111.6 KB | Display | PDB format |
PDBx/mmJSON format | 6x8e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x8e_validation.pdf.gz | 978.9 KB | Display | wwPDB validaton report |
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Full document | 6x8e_full_validation.pdf.gz | 982.4 KB | Display | |
Data in XML | 6x8e_validation.xml.gz | 28 KB | Display | |
Data in CIF | 6x8e_validation.cif.gz | 41.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x8/6x8e ftp://data.pdbj.org/pub/pdb/validation_reports/x8/6x8e | HTTPS FTP |
-Related structure data
Related structure data | 6x8fC 6x8gC 2b7aS 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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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 35033.684 Da / Num. of mol.: 2 / Fragment: kinase domain / Mutation: M1073S, F1076T Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Cell line (production host): Sf21 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O60674, non-specific protein-tyrosine kinase #2: Chemical | #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: 2.01 Å3/Da / Density % sol: 38.7 % / Mosaicity: 0.15 ° |
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Crystal grow | Temperature: 298 K / Method: evaporation / pH: 7.5 Details: 0.1 M HEPES pH 7.5, 0.1 M sodium acetate trihydrate, and 30-35% PEG-3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 14, 2014 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.75→153.75 Å / Num. obs: 45549 / % possible obs: 81.9 % / Redundancy: 2.7 % / Biso Wilson estimate: 22.1 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.057 / Rpim(I) all: 0.039 / Rrim(I) all: 0.069 / Net I/σ(I): 14.2 / Num. measured all: 121084 / Scaling rejects: 1 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2B7A Resolution: 1.75→76.88 Å / Cor.coef. Fo:Fc: 0.9355 / Cor.coef. Fo:Fc free: 0.9118 / SU R Cruickshank DPI: 0.155 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.16 / SU Rfree Blow DPI: 0.144 / SU Rfree Cruickshank DPI: 0.142
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Displacement parameters | Biso max: 109.71 Å2 / Biso mean: 28.04 Å2 / Biso min: 5.77 Å2
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Refine analyze | Luzzati coordinate error obs: 0.207 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.75→76.88 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.75→1.79 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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