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- PDB-4gii: Tyk2 (JH1) in complex with 2,6-dichloro-4-cyano-N-{2-[(cyclopropy... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4gii | ||||||
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Title | Tyk2 (JH1) in complex with 2,6-dichloro-4-cyano-N-{2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}benzamide | ||||||
![]() | Non-receptor tyrosine-protein kinase TYK2 | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / Aminopyridine / Benzamide / Kinase / Enzyme inhibitor / Tyrosine Kinase / ATP Binding / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() type III interferon-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / Interleukin-35 Signalling ...type III interferon-mediated signaling pathway / interleukin-12 receptor complex / interleukin-23 receptor complex / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Ultsch, M.H. | ||||||
![]() | ![]() Title: Lead Optimization of a 4-Aminopyridine Benzamide Scaffold To Identify Potent, Selective, and Orally Bioavailable TYK2 Inhibitors. Authors: Liang, J. / van Abbema, A. / Balazs, M. / Barrett, K. / Berezhkovsky, L. / Blair, W. / Chang, C. / Delarosa, D. / Devoss, J. / Driscoll, J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / ...Authors: Liang, J. / van Abbema, A. / Balazs, M. / Barrett, K. / Berezhkovsky, L. / Blair, W. / Chang, C. / Delarosa, D. / Devoss, J. / Driscoll, J. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / Halladay, J. / Johnson, A. / Kohli, P.B. / Lai, Y. / Liu, Y. / Lyssikatos, J. / Mantik, P. / Menghrajani, K. / Murray, J. / Peng, I. / Sambrone, A. / Shia, S. / Shin, Y. / Smith, J. / Sohn, S. / Tsui, V. / Ultsch, M. / Wu, L.C. / Xiao, Y. / Yang, W. / Young, J. / Zhang, B. / Zhu, B.Y. / Magnuson, S. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 133.8 KB | Display | ![]() |
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PDB format | ![]() | 103.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 702.1 KB | Display | ![]() |
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Full document | ![]() | 704.5 KB | Display | |
Data in XML | ![]() | 12.8 KB | Display | |
Data in CIF | ![]() | 16.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4gj2C ![]() 4gj3C ![]() 3nz0S C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 34748.734 Da / Num. of mol.: 1 / Fragment: Kinase domain, UNP residues 885-1176 / Mutation: C936A,Q969A,E971A,K972A,D1023N,C1142A Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P29597, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-0X6 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.03 Å3/Da / Density % sol: 39.27 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 20-25%(w/v) PEG3350 and 0.2M Mg sulfate, 0.1M MES pH6.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K |
-Data collection
Diffraction | Mean temperature: 173 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Apr 11, 2012 |
Radiation | Monochromator: ide scattering bent cube-root I-beam single crystal; asymmetric cut 4.965 degs Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→37.1 Å / Num. obs: 12062 / % possible obs: 93.6 % / Observed criterion σ(I): 3.5 / Redundancy: 4.2 % / Biso Wilson estimate: 39.07 Å2 / Rmerge(I) obs: 0.063 / Net I/σ(I): 16.4 |
Reflection shell | Resolution: 2.31→2.43 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.398 / Mean I/σ(I) obs: 3.5 / Num. unique all: 1765 / % possible all: 95.2 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3NZ0 Resolution: 2.31→37.1 Å / Cor.coef. Fo:Fc: 0.9232 / Cor.coef. Fo:Fc free: 0.9134 / SU R Cruickshank DPI: 0.528 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso mean: 54.98 Å2
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Refine analyze | Luzzati coordinate error obs: 0.384 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.31→37.1 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.31→2.53 Å / Total num. of bins used: 6
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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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