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Yorodumi- PDB-7k7q: CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN)... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7k7q | ||||||
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Title | CRYSTAL STRUCTURE OF TYROSINE KINASE 2 JH2 (PSEUDO KINASE DOMAIN) COMPLEXED WITH COMPOUND-12 AKA:6-[(cyclopropanecarbonyl)amino]-4-({3-[6-(dimethylcarbamoyl)pyridazin-3-yl]-2-methoxyphenyl}amino)-N-methylpyridazine-3-carboxamide | ||||||
Components | Non-receptor tyrosine-protein kinase TYK2 | ||||||
Keywords | TRANSFERASE / KINASE / TYK2 / PSEUDOKINASE | ||||||
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: 2.27 Å | ||||||
Authors | Khan, J.A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2. Authors: Liu, C. / Lin, J. / Langevine, C. / Smith, D. / Li, J. / Tokarski, J.S. / Khan, J. / Ruzanov, M. / Strnad, J. / Zupa-Fernandez, A. / Cheng, L. / Gillooly, K.M. / Shuster, D. / Zhang, Y. / ...Authors: Liu, C. / Lin, J. / Langevine, C. / Smith, D. / Li, J. / Tokarski, J.S. / Khan, J. / Ruzanov, M. / Strnad, J. / Zupa-Fernandez, A. / Cheng, L. / Gillooly, K.M. / Shuster, D. / Zhang, Y. / Thankappan, A. / McIntyre, K.W. / Chaudhry, C. / Elzinga, P.A. / Chiney, M. / Chimalakonda, A. / Lombardo, L.J. / Macor, J.E. / Carter, P.H. / Burke, J.R. / Weinstein, D.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7k7q.cif.gz | 121.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7k7q.ent.gz | 91 KB | Display | PDB format |
PDBx/mmJSON format | 7k7q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k7/7k7q ftp://data.pdbj.org/pub/pdb/validation_reports/k7/7k7q | HTTPS FTP |
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-Related structure data
Related structure data | 7k7oC 6nslS 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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Unit cell |
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-Components
#1: Protein | Mass: 35499.156 Da / Num. of mol.: 2 / Fragment: TYK2-JH2 DOMAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TYK2 / Plasmid: pFastBac1 / Cell line (production host): Sf9 / 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: 2.25 Å3/Da / Density % sol: 45.41 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 200 mM ammonium sulfate, and 100 mM Cacodylate buffer, pH 7.5, 30%(W/V) PEG 5000 (Methyl Ether) |
-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: Oct 4, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.27→47.75 Å / Num. obs: 28974 / % possible obs: 99.2 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.05 / Net I/σ(I): 13.2 |
Reflection shell | Resolution: 2.27→2.62 Å / Rmerge(I) obs: 0.32 / Mean I/σ(I) obs: 3.2 / Num. unique obs: 10115 / % possible all: 99.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6NSL Resolution: 2.27→28.3 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.9407 / SU R Cruickshank DPI: 0.253 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.247 / SU Rfree Blow DPI: 0.183 / SU Rfree Cruickshank DPI: 0.186
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Displacement parameters | Biso max: 151.72 Å2 / Biso mean: 45.62 Å2 / Biso min: 24.41 Å2
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Refine analyze | Luzzati coordinate error obs: 0.262 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.27→28.3 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.27→2.35 Å / Rfactor Rfree error: 0 / Total num. of bins used: 15
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