+Open data
-Basic information
Entry | Database: PDB / ID: 6n79 | ||||||
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Title | Structure of the human JAK1 kinase domain with compound 20 | ||||||
Components | Tyrosine-protein kinase JAK1 | ||||||
Keywords | IMMUNE SYSTEM / JAK1 / IL13 / IL-13 / JAK2 / JAK3 / TYK2 | ||||||
Function / homology | Function and homology information protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / T-helper 17 cell lineage commitment / positive regulation of homotypic cell-cell adhesion / type III interferon-mediated signaling pathway / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway ...protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / T-helper 17 cell lineage commitment / positive regulation of homotypic cell-cell adhesion / type III interferon-mediated signaling pathway / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / interleukin-2-mediated signaling pathway / interleukin-15-mediated signaling pathway / Interleukin-15 signaling / Interleukin-12 signaling / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-2 signaling / growth hormone receptor binding / Other interleukin signaling / IFNG signaling activates MAPKs / Interleukin-20 family signaling / type I interferon-mediated signaling pathway / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / positive regulation of sprouting angiogenesis / MAPK3 (ERK1) activation / Interleukin-10 signaling / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / Signaling by CSF3 (G-CSF) / extrinsic component of cytoplasmic side of plasma membrane / Interleukin-7 signaling / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / cytoplasmic side of plasma membrane / ISG15 antiviral mechanism / cellular response to virus / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / Interferon gamma signaling / Interferon alpha/beta signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell differentiation / cytoskeleton / endosome / intracellular signal transduction / response to antibiotic / protein phosphorylation / focal adhesion / ubiquitin protein ligase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.27 Å | ||||||
Authors | Lupardus, P.J. / Brown, D. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2019 Title: Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling. Authors: Zak, M. / Hanan, E.J. / Lupardus, P. / Brown, D.G. / Robinson, C. / Siu, M. / Lyssikatos, J.P. / Romero, F.A. / Zhao, G. / Kellar, T. / Mendonca, R. / Ray, N.C. / Goodacre, S.C. / Crackett, ...Authors: Zak, M. / Hanan, E.J. / Lupardus, P. / Brown, D.G. / Robinson, C. / Siu, M. / Lyssikatos, J.P. / Romero, F.A. / Zhao, G. / Kellar, T. / Mendonca, R. / Ray, N.C. / Goodacre, S.C. / Crackett, P.H. / McLean, N. / Hurley, C.A. / Yuen, P.W. / Cheng, Y.X. / Liu, X. / Liimatta, M. / Kohli, P.B. / Nonomiya, J. / Salmon, G. / Buckley, G. / Lloyd, J. / Gibbons, P. / Ghilardi, N. / Kenny, J.R. / Johnson, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6n79.cif.gz | 71.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6n79.ent.gz | 54.9 KB | Display | PDB format |
PDBx/mmJSON format | 6n79.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/n7/6n79 ftp://data.pdbj.org/pub/pdb/validation_reports/n7/6n79 | HTTPS FTP |
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-Related structure data
Related structure data | 6n77C 6n78C 6n7aC 6n7bC 6n7cC 6n7dC 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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Unit cell |
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-Components
#1: Protein | Mass: 34746.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK1, JAK1A, JAK1B / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P23458, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-KES / |
#3: Chemical | ChemComp-GOL / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.34 Å3/Da / Density % sol: 47.45 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 5.5 / Details: 0.1 M MES pH 5-6 and 25-35% PEG 6000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Oct 14, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.27→44.83 Å / Num. obs: 15855 / % possible obs: 99.9 % / Redundancy: 6.2 % / Biso Wilson estimate: 46.47 Å2 / CC1/2: 0.993 / Rmerge(I) obs: 0.124 / Net I/σ(I): 9.7 |
Reflection shell | Resolution: 2.27→2.33 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.688 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 1134 / CC1/2: 0.799 / % possible all: 100 |
-Processing
Software |
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Refinement | Resolution: 2.27→44.83 Å / Cor.coef. Fo:Fc: 0.914 / Cor.coef. Fo:Fc free: 0.873 / SU R Cruickshank DPI: 0.315 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.338 / SU Rfree Blow DPI: 0.242 / SU Rfree Cruickshank DPI: 0.238
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Displacement parameters | Biso mean: 41.59 Å2
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Refine analyze | Luzzati coordinate error obs: 0.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.27→44.83 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.27→2.43 Å / Total num. of bins used: 8
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