+Open data
-Basic information
Entry | Database: PDB / ID: 6rsu | ||||||
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Title | TBK1 in complex with Inhibitor compound 35 | ||||||
Components | Serine/threonine-protein kinase TBK1 | ||||||
Keywords | IMMUNE SYSTEM / kinase / innate immunity / small molecule inhibitor | ||||||
Function / homology | Function and homology information IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / dendritic cell proliferation / regulation of type I interferon production / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / cGAS/STING signaling pathway ...IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / dendritic cell proliferation / regulation of type I interferon production / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / cGAS/STING signaling pathway / TNFR1-induced proapoptotic signaling / toll-like receptor 4 signaling pathway / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / antiviral innate immune response / positive regulation of macroautophagy / positive regulation of type I interferon production / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of autophagy / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / TICAM1-dependent activation of IRF3/IRF7 / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Negative regulators of DDX58/IFIH1 signaling / phosphoprotein binding / Regulation of TNFR1 signaling / peptidyl-threonine phosphorylation / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of peptidyl-serine phosphorylation / TRAF3-dependent IRF activation pathway / peptidyl-serine phosphorylation / protein phosphatase binding / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / Potential therapeutics for SARS / nucleic acid binding / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / protein kinase activity / inflammatory response / protein phosphorylation / negative regulation of gene expression / intracellular membrane-bounded organelle / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / SARS-CoV-2 activates/modulates innate and adaptive immune responses / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / identical protein binding / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.75 Å | ||||||
Authors | Panne, D. / Hillig, R.C. / Rengachari, S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of BAY-985, a Highly Selective TBK1/IKK epsilon Inhibitor. Authors: Lefranc, J. / Schulze, V.K. / Hillig, R.C. / Briem, H. / Prinz, F. / Mengel, A. / Heinrich, T. / Balint, J. / Rengachari, S. / Irlbacher, H. / Stockigt, D. / Bomer, U. / Bader, B. / Gradl, S. ...Authors: Lefranc, J. / Schulze, V.K. / Hillig, R.C. / Briem, H. / Prinz, F. / Mengel, A. / Heinrich, T. / Balint, J. / Rengachari, S. / Irlbacher, H. / Stockigt, D. / Bomer, U. / Bader, B. / Gradl, S.N. / Nising, C.F. / von Nussbaum, F. / Mumberg, D. / Panne, D. / Wengner, A.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6rsu.cif.gz | 311.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rsu.ent.gz | 205 KB | Display | PDB format |
PDBx/mmJSON format | 6rsu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6rsu_validation.pdf.gz | 715 KB | Display | wwPDB validaton report |
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Full document | 6rsu_full_validation.pdf.gz | 773 KB | Display | |
Data in XML | 6rsu_validation.xml.gz | 32.8 KB | Display | |
Data in CIF | 6rsu_validation.cif.gz | 42.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rs/6rsu ftp://data.pdbj.org/pub/pdb/validation_reports/rs/6rsu | HTTPS FTP |
-Related structure data
Related structure data | 6rsrC 6rstC 4iwoS 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: 76170.055 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TBK1, NAK / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q9UHD2, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-KJB / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.26 Å3/Da / Density % sol: 62.28 % |
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Crystal grow | Temperature: 294 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 100 mM HEPES pH 7.5, 5-8% PEG 8000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.966 Å |
Detector | Type: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Dec 11, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.966 Å / Relative weight: 1 |
Reflection | Resolution: 2.74→48.9 Å / Num. obs: 19151 / % possible obs: 99.4 % / Redundancy: 6.7 % / Biso Wilson estimate: 98.98 Å2 / CC1/2: 0.61 / Net I/σ(I): 15.7 |
Reflection shell | Resolution: 2.74→2.94 Å / Num. unique obs: 912 / Rrim(I) all: 123 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4IWO Resolution: 2.75→48.9 Å / SU ML: 0.402 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 48.9147
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 85.74 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.75→48.9 Å
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Refine LS restraints |
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LS refinement shell |
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