+Open data
-Basic information
Entry | Database: PDB / ID: 6thx | ||||||
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Title | IRAK4 in complex with inhibitor | ||||||
Components | Interleukin-1 receptor-associated kinase 4 | ||||||
Keywords | SIGNALING PROTEIN / IRAK4 / kinase / inhibitor / cancer | ||||||
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: 1.99 Å | ||||||
Authors | Xue, Y. / Aagaard, A. / Degorce, S.L. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2020 Title: Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors. Authors: Degorce, S.L. / Aagaard, A. / Anjum, R. / Cumming, I.A. / Diene, C.R. / Fallan, C. / Johnson, T. / Leuchowius, K.J. / Orton, A.L. / Pearson, S. / Robb, G.R. / Rosen, A. / Scarfe, G.B. / ...Authors: Degorce, S.L. / Aagaard, A. / Anjum, R. / Cumming, I.A. / Diene, C.R. / Fallan, C. / Johnson, T. / Leuchowius, K.J. / Orton, A.L. / Pearson, S. / Robb, G.R. / Rosen, A. / Scarfe, G.B. / Scott, J.S. / Smith, J.M. / Steward, O.R. / Terstiege, I. / Tucker, M.J. / Turner, P. / Wilkinson, S.D. / Wrigley, G.L. / Xue, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6thx.cif.gz | 243.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6thx.ent.gz | 196.8 KB | Display | PDB format |
PDBx/mmJSON format | 6thx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6thx_validation.pdf.gz | 957.6 KB | Display | wwPDB validaton report |
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Full document | 6thx_full_validation.pdf.gz | 973.8 KB | Display | |
Data in XML | 6thx_validation.xml.gz | 25.3 KB | Display | |
Data in CIF | 6thx_validation.cif.gz | 34.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/th/6thx ftp://data.pdbj.org/pub/pdb/validation_reports/th/6thx | HTTPS FTP |
-Related structure data
Related structure data | 6thwC 6thzC 6ti8C 6tiaC 6rfjS 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 34635.008 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Residue TPO is phosphorylated THR, residue SEP is phosphorylated SER. 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: 2.68 Å3/Da / Density % sol: 54.17 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop Details: 25 mM HEPES pH 7.5, 1 mM EDTA, 1 mM TCEP, 5% Glycerol, 150 mM NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.979 Å |
Detector | Type: DECTRIS PILATUS 12M / Detector: PIXEL / Date: Mar 28, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 1.99→86.62 Å / Num. obs: 46995 / % possible obs: 100 % / Redundancy: 6.6 % / Rmerge(I) obs: 0.054 / Rpim(I) all: 0.023 / Rrim(I) all: 0.059 / Net I/σ(I): 14.2 |
Reflection shell | Resolution: 1.99→2.04 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.587 / Mean I/σ(I) obs: 3 / Num. unique obs: 3427 / Rpim(I) all: 0.247 / Rrim(I) all: 0.638 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6rfj Resolution: 1.99→71.09 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.924 / SU R Cruickshank DPI: 0.187 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.188 / SU Rfree Blow DPI: 0.159 / SU Rfree Cruickshank DPI: 0.159
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Displacement parameters | Biso max: 181.95 Å2 / Biso mean: 66.54 Å2 / Biso min: 29.55 Å2
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Refine analyze | Luzzati coordinate error obs: 0.33 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.99→71.09 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.99→2.01 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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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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