+Open data
-Basic information
Entry | Database: PDB / ID: 8w3x | ||||||
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Title | Crystal structure of IRAK4 in complex with compound 6 | ||||||
Components | Interleukin-1 receptor-associated kinase 4 | ||||||
Keywords | TRANSFERASE / INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 | ||||||
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 / interleukin-1-mediated signaling pathway / MyD88-dependent toll-like receptor 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 / positive regulation of canonical NF-kappaB signal transduction / cellular response to lipopolysaccharide / endosome membrane / non-specific serine/threonine protein kinase / intracellular signal transduction / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / protein kinase binding / magnesium ion binding / cell surface / 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: 1.765 Å | ||||||
Authors | Han, S. / Knafels, J.D. | ||||||
Funding support | 1items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2024 Title: In Retrospect: Root-Cause Analysis of Structure-Activity Relationships in IRAK4 Inhibitor Zimlovisertib (PF-06650833). Authors: Wright, S.W. / Farley, K.A. / Han, S. / Knafels, J.D. / Lee, K.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8w3x.cif.gz | 481.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8w3x.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8w3x.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8w3x_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8w3x_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8w3x_validation.xml.gz | 50.7 KB | Display | |
Data in CIF | 8w3x_validation.cif.gz | 72.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w3/8w3x ftp://data.pdbj.org/pub/pdb/validation_reports/w3/8w3x | HTTPS FTP |
-Related structure data
Related structure data | 8w3wC 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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2 |
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3 |
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4 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 36584.020 Da / Num. of mol.: 4 / Fragment: UNP residues 154-460 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-A1AFH / Mass: 329.350 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C17H19N3O4 / Feature type: SUBJECT OF INVESTIGATION #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: 2.47 Å3/Da / Density % sol: 50.12 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / Details: AMMONIUM CITRATE |
-Data collection
Diffraction | Mean temperature: 173 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 2M / Detector: PIXEL / Date: May 3, 2023 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.765→48.94 Å / Num. obs: 127742 / % possible obs: 95.1 % / Redundancy: 3.4 % / CC1/2: 0.999 / Net I/σ(I): 12.2 |
Reflection shell | Resolution: 1.765→1.8 Å / Num. unique obs: 4207 / CC1/2: 0.591 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.765→48.94 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.953 / SU R Cruickshank DPI: 0.116 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.117 / SU Rfree Blow DPI: 0.107 / SU Rfree Cruickshank DPI: 0.107 Details: HYDROGENS WERE FULLY REFINED WITH ZERO OCCUPANCY AT NUCLEAR POSITION.
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Displacement parameters | Biso mean: 37.62 Å2
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Refine analyze | Luzzati coordinate error obs: 0.23 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.765→48.94 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.765→1.79 Å
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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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