+Open data
-Basic information
Entry | Database: PDB / ID: 8br5 | ||||||
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Title | Discovery of IRAK4 Inhibitor 41 | ||||||
Components | Interleukin-1 receptor-associated kinase 4 | ||||||
Keywords | TRANSFERASE / IRAK4 / KINASE | ||||||
Function / homology | Function and homology information IRAK4 deficiency (TLR5) / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / neutrophil migration / interleukin-33-mediated signaling pathway / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding ...IRAK4 deficiency (TLR5) / MyD88 dependent cascade initiated on endosome / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / neutrophil migration / interleukin-33-mediated signaling pathway / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / toll-like receptor 4 signaling pathway / toll-like receptor signaling pathway / extrinsic component of plasma membrane / JNK cascade / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / positive regulation of smooth muscle cell proliferation / cytokine-mediated signaling pathway / Interleukin-1 signaling / PIP3 activates AKT signaling / kinase activity / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cellular response to lipopolysaccharide / positive regulation of canonical NF-kappaB signal transduction / phosphorylation / non-specific serine/threonine protein kinase / endosome membrane / intracellular signal transduction / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / protein kinase binding / cell surface / magnesium ion binding / extracellular space / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Schafer, M. / Bothe, U. / Schmidt, N. / Gunther, J. / Nubbemeyer, R. / Siebeneicher, H. / Ring, S. / Boemer, U. / Peters, M. / Denner, K. ...Schafer, M. / Bothe, U. / Schmidt, N. / Gunther, J. / Nubbemeyer, R. / Siebeneicher, H. / Ring, S. / Boemer, U. / Peters, M. / Denner, K. / Himmel, H. / Sutter, A. / Terebesi, I. / Lange, M. / Wenger, A.M. / Guimond, N. / Thaler, T. / Platzek, J. / Eberspaecher, U. / Steuber, H. / Steinmeyer, A. / Zollner, T.M. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839 . Authors: Bothe, U. / Gunther, J. / Nubbemeyer, R. / Siebeneicher, H. / Ring, S. / Bomer, U. / Peters, M. / Rausch, A. / Denner, K. / Himmel, H. / Sutter, A. / Terebesi, I. / Lange, M. / Wengner, A.M. ...Authors: Bothe, U. / Gunther, J. / Nubbemeyer, R. / Siebeneicher, H. / Ring, S. / Bomer, U. / Peters, M. / Rausch, A. / Denner, K. / Himmel, H. / Sutter, A. / Terebesi, I. / Lange, M. / Wengner, A.M. / Guimond, N. / Thaler, T. / Platzek, J. / Eberspacher, U. / Schafer, M. / Steuber, H. / Zollner, T.M. / Steinmeyer, A. / Schmidt, N. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8br5.cif.gz | 248.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8br5.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8br5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8br5_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 8br5_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 8br5_validation.xml.gz | 44.2 KB | Display | |
Data in CIF | 8br5_validation.cif.gz | 57.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/br/8br5 ftp://data.pdbj.org/pub/pdb/validation_reports/br/8br5 | HTTPS FTP |
-Related structure data
Related structure data | 8atbC 8atlC 8atnC 8br6C 8br7C C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: End auth comp-ID: ALA / End label comp-ID: ALA
NCS ensembles :
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-Components
#1: Protein | Mass: 33769.984 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase #2: Chemical | ChemComp-R73 / ~{ #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: 2.77 Å3/Da / Density % sol: 55.53 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: none |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 30, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→90.583 Å / Num. obs: 39488 / % possible obs: 99.3 % / Redundancy: 4.42 % / CC1/2: 0.998 / Rrim(I) all: 0.094 / Net I/σ(I): 16.8 |
Reflection shell | Resolution: 2.7→2.95 Å / Mean I/σ(I) obs: 3.58 / Num. unique obs: 9173 / CC1/2: 0.882 / Rrim(I) all: 0.523 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: in house model Resolution: 2.7→90.583 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.895 / SU B: 15.677 / SU ML: 0.299 / Cross valid method: THROUGHOUT / ESU R: 1.54 / ESU R Free: 0.34 Details: Hydrogens have been added in their riding positions
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 57.762 Å2
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Refinement step | Cycle: LAST / Resolution: 2.7→90.583 Å
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Refine LS restraints |
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