+Open data
-Basic information
Entry | Database: PDB / ID: 7qg1 | ||||||
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Title | IRAK4 in complex with inhibitor | ||||||
Components | Interleukin-1 receptor-associated kinase 4 | ||||||
Keywords | TRANSFERASE / Kinase inhibitor Interleukin-1 Receptor-Associated Kinase 4 Interleukin-1 signaling | ||||||
Function / homology | Function and homology information MyD88 dependent cascade initiated on endosome / IRAK4 deficiency (TLR5) / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / interleukin-33-mediated signaling pathway / neutrophil migration / toll-like receptor 9 signaling pathway / neutrophil mediated immunity / interleukin-1 receptor binding ...MyD88 dependent cascade initiated on endosome / IRAK4 deficiency (TLR5) / TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation / MyD88 cascade initiated on plasma membrane / Toll signaling pathway / interleukin-33-mediated signaling pathway / neutrophil migration / 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 / cellular response to lipopolysaccharide / positive regulation of canonical NF-kappaB signal transduction / 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 / magnesium ion binding / cell surface / extracellular space / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.07 Å | ||||||
Authors | Xue, Y. / Aagaard, A. / Robb, G.R. / Degorce, S.L. | ||||||
Funding support | Sweden, 1items
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Citation | Journal: Bioorg.Med.Chem. / Year: 2022 Title: Identification and optimisation of a pyrimidopyridone series of IRAK4 inhibitors. Authors: Cumming, I.A. / Degorce, S.L. / Aagaard, A. / Braybrooke, E.L. / Davies, N.L. / Diene, C.R. / Eatherton, A.J. / Felstead, H.R. / Groombridge, S.D. / Lenz, E.M. / Li, Y. / Nai, Y. / Pearson, ...Authors: Cumming, I.A. / Degorce, S.L. / Aagaard, A. / Braybrooke, E.L. / Davies, N.L. / Diene, C.R. / Eatherton, A.J. / Felstead, H.R. / Groombridge, S.D. / Lenz, E.M. / Li, Y. / Nai, Y. / Pearson, S. / Robb, G.R. / Scott, J.S. / Steward, O.R. / Wu, C. / Xue, Y. / Zhang, L. / Zhang, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7qg1.cif.gz | 130.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7qg1.ent.gz | 99.1 KB | Display | PDB format |
PDBx/mmJSON format | 7qg1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7qg1_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7qg1_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7qg1_validation.xml.gz | 25.6 KB | Display | |
Data in CIF | 7qg1_validation.cif.gz | 35.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qg/7qg1 ftp://data.pdbj.org/pub/pdb/validation_reports/qg/7qg1 | HTTPS FTP |
-Related structure data
Related structure data | 7qg2C 7qg3C 7qg5C 6rfjS S: Starting model for refinement 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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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 36528.082 Da / Num. of mol.: 2 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 | #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: 2.34 Å3/Da / Density % sol: 47.39 % |
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Crystal grow | Temperature: 298 K / Method: evaporation / Details: Ammonium sulfate 0.1 M Hepes pH 6.8-7.4 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Feb 9, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.07→86.75 Å / Num. obs: 41936 / % possible obs: 99.9 % / Redundancy: 7.8 % / Biso Wilson estimate: 48.53 Å2 / Rmerge(I) obs: 0.057 / Net I/σ(I): 16.3 |
Reflection shell | Resolution: 2.07→2.18 Å / Redundancy: 6.5 % / Rmerge(I) obs: 1.266 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 6032 / % possible all: 99.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6RFJ Resolution: 2.07→86.75 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.898 / Rfactor Rfree error: 0.2 / SU R Cruickshank DPI: 0.228 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.233 / SU Rfree Blow DPI: 0.197 / SU Rfree Cruickshank DPI: 0.196
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Displacement parameters | Biso max: 192.6 Å2 / Biso mean: 68.73 Å2 / Biso min: 27.89 Å2
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Refine analyze | Luzzati coordinate error obs: 0.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.07→86.75 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.07→2.12 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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