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Yorodumi- PDB-4gfo: TYK2 kinase (JH1 domain) with 2,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPY... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4gfo | ||||||
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Title | TYK2 kinase (JH1 domain) with 2,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPYRIDIN-4-YL)BENZAMIDE | ||||||
Components | Non-receptor tyrosine-protein kinase TYK2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / protein kinase / phosphotransfer catalyst / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information type III interferon-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 ...type III interferon-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 / 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 / Interferon alpha/beta signaling / positive regulation of type II interferon production / 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 / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å | ||||||
Authors | Eigenbrot, C. / Ultsch, M. | ||||||
Citation | Journal: Eur.J.Med.Chem. / Year: 2013 Title: Lead identification of novel and selective TYK2 inhibitors. Authors: Liang, J. / Tsui, V. / Van Abbema, A. / Bao, L. / Barrett, K. / Beresini, M. / Berezhkovskiy, L. / Blair, W.S. / Chang, C. / Driscoll, J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / ...Authors: Liang, J. / Tsui, V. / Van Abbema, A. / Bao, L. / Barrett, K. / Beresini, M. / Berezhkovskiy, L. / Blair, W.S. / Chang, C. / Driscoll, J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / Halladay, J. / Johnson, A. / Kohli, P.B. / Lai, Y. / Liimatta, M. / Mantik, P. / Menghrajani, K. / Murray, J. / Sambrone, A. / Xiao, Y. / Shia, S. / Shin, Y. / Smith, J. / Sohn, S. / Stanley, M. / Ultsch, M. / Zhang, B. / Wu, L.C. / Magnuson, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4gfo.cif.gz | 135.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4gfo.ent.gz | 105.1 KB | Display | PDB format |
PDBx/mmJSON format | 4gfo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4gfo_validation.pdf.gz | 801.5 KB | Display | wwPDB validaton report |
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Full document | 4gfo_full_validation.pdf.gz | 805.3 KB | Display | |
Data in XML | 4gfo_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | 4gfo_validation.cif.gz | 17.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gf/4gfo ftp://data.pdbj.org/pub/pdb/validation_reports/gf/4gfo | HTTPS FTP |
-Related structure data
Related structure data | 4gfmC 4gihC 4gmyC 4gvjC 3nz0S C: citing same article (ref.) S: Starting model for refinement |
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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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 35002.059 Da / Num. of mol.: 1 / Fragment: JH1 domain, UNP residues 884-1176 / Mutation: D1023N Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TYK2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P29597, non-specific protein-tyrosine kinase |
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-Non-polymers , 5 types, 84 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-GOL / | #5: Chemical | ChemComp-0X2 / | #6: Water | ChemComp-HOH / | |
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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: 2.11 Å3/Da / Density % sol: 41.8 % |
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Crystal grow | Temperature: 300 K / Method: vapor diffusion, sitting drop / pH: 5 Details: 2 M ammonium sulfate, pH 5, VAPOR DIFFUSION, SITTING DROP, temperature 300K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 0.98 Å |
Detector | Type: MARMOSAIC 325 mm CCD / Detector: CCD / Date: Nov 13, 2008 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. all: 171418 / Num. obs: 171418 / % possible obs: 92.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 12 % / Biso Wilson estimate: 41.01 Å2 / Rsym value: 0.072 / Net I/σ(I): 39 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3NZ0 Resolution: 2.3→42.53 Å / Cor.coef. Fo:Fc: 0.914 / Cor.coef. Fo:Fc free: 0.8673 / SU R Cruickshank DPI: 0.423 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso mean: 50.75 Å2
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Refine analyze | Luzzati coordinate error obs: 0.454 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3→42.53 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.3→2.48 Å / Total num. of bins used: 7
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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