+Open data
-Basic information
Entry | Database: PDB / ID: 7qg3 | ||||||
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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 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: 2.11 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 | 7qg3.cif.gz | 126.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7qg3.ent.gz | 96.6 KB | Display | PDB format |
PDBx/mmJSON format | 7qg3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7qg3_validation.pdf.gz | 940 KB | Display | wwPDB validaton report |
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Full document | 7qg3_full_validation.pdf.gz | 954.6 KB | Display | |
Data in XML | 7qg3_validation.xml.gz | 23.3 KB | Display | |
Data in CIF | 7qg3_validation.cif.gz | 30.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qg/7qg3 ftp://data.pdbj.org/pub/pdb/validation_reports/qg/7qg3 | HTTPS FTP |
-Related structure data
Related structure data | 7qg1C 7qg2C 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: 34714.988 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: 2.48 Å3/Da / Density % sol: 50.35 % |
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Crystal grow | Temperature: 298 K / Method: evaporation / Details: 2.7 M AMS 0.1 M Hepes pH 7.1-7.7 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.976 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 7, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 2.11→49.37 Å / Num. obs: 39631 / % possible obs: 99.5 % / Redundancy: 8.1 % / Biso Wilson estimate: 55.53 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.085 / Rpim(I) all: 0.037 / Rrim(I) all: 0.093 / Net I/σ(I): 9.8 |
Reflection shell | Resolution: 2.11→2.19 Å / Redundancy: 5.9 % / Mean I/σ(I) obs: 0.7 / Num. unique obs: 3712 / CC1/2: 0.364 / % possible all: 95.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6RFJ Resolution: 2.11→44.42 Å / Cor.coef. Fo:Fc: 0.915 / Cor.coef. Fo:Fc free: 0.903 / SU R Cruickshank DPI: 0.285 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.277 / SU Rfree Blow DPI: 0.223 / SU Rfree Cruickshank DPI: 0.228
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Displacement parameters | Biso max: 217.08 Å2 / Biso min: 29.54 Å2
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Refine analyze | Luzzati coordinate error obs: 0.49 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.11→44.42 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.11→2.17 Å / Rfactor Rfree error: 0 / Total num. of bins used: 19
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