+Open data
-Basic information
Entry | Database: PDB / ID: 6x8f | ||||||
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Title | Crystal structure of TYK2 with Compound 11 | ||||||
Components | Non-receptor tyrosine-protein kinase TYK2 | ||||||
Keywords | TRANSFERASE / kinase | ||||||
Function / homology | Function and homology information type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / Interleukin-12 signaling ...type III interferon-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of natural killer cell proliferation / growth hormone receptor binding / Other interleukin signaling / extrinsic component of plasma membrane / Interleukin-20 family signaling / type I interferon-mediated signaling pathway / Interleukin-6 signaling / MAPK3 (ERK1) activation / positive regulation of interleukin-17 production / Interleukin-10 signaling / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / type II interferon-mediated signaling pathway / positive regulation of T cell proliferation / Signaling by CSF3 (G-CSF) / non-specific protein-tyrosine kinase / positive regulation of receptor signaling pathway via JAK-STAT / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / cytoplasmic side of plasma membrane / cellular response to virus / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / positive regulation of type II interferon production / Interferon alpha/beta signaling / Signaling by ALK fusions and activated point mutants / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell differentiation / cytoskeleton / intracellular signal transduction / immune response / protein phosphorylation / SARS-CoV-2 activates/modulates innate and adaptive immune responses / extracellular exosome / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 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 | 6x8f.cif.gz | 137.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6x8f.ent.gz | 105 KB | Display | PDB format |
PDBx/mmJSON format | 6x8f.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x8/6x8f ftp://data.pdbj.org/pub/pdb/validation_reports/x8/6x8f | HTTPS FTP |
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-Related structure data
Related structure data | 6x8eC 6x8gC 3lxpS 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: 36550.570 Da / Num. of mol.: 2 / Fragment: kinase domain / Mutation: C936A, C1142A, Q969A, E971A, K972A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TYK2 / Cell line (production host): Sf21 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P29597, 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: 1.84 Å3/Da / Density % sol: 33.09 % / Mosaicity: 0.46 ° |
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Crystal grow | Temperature: 298 K / Method: evaporation / pH: 8 Details: 0.1 M bis-tris pH 5.5, 0.25 M NaCl, 10 mM TCEP, 27-33% 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: Mar 6, 2014 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.15→74.26 Å / Num. obs: 24732 / % possible obs: 83 % / Redundancy: 2.9 % / Biso Wilson estimate: 26.94 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.083 / Rpim(I) all: 0.057 / Rrim(I) all: 0.101 / Net I/σ(I): 161.4 / Num. measured all: 70912 / Scaling rejects: 17 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3LXP Resolution: 2.15→50.12 Å / Cor.coef. Fo:Fc: 0.8942 / Cor.coef. Fo:Fc free: 0.8568 / SU R Cruickshank DPI: 0.704 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.721 / SU Rfree Blow DPI: 0.281 / SU Rfree Cruickshank DPI: 0.284
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Displacement parameters | Biso max: 133.39 Å2 / Biso mean: 41.27 Å2 / Biso min: 6.77 Å2
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Refine analyze | Luzzati coordinate error obs: 0.314 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.15→50.12 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.15→2.25 Å / Rfactor Rfree error: 0 / Total num. of bins used: 11
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