+Open data
-Basic information
Entry | Database: PDB / ID: 4yp8 | ||||||
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Title | Irak4-inhibitor co-structure | ||||||
Components | Interleukin-1 receptor-associated kinase 4 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / KINASE / PHOSPHATASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX | ||||||
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: 2.641 Å | ||||||
Authors | Fischmann, T.O. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2015 Title: Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation. Authors: McElroy, W.T. / Tan, Z. / Ho, G. / Paliwal, S. / Li, G. / Seganish, W.M. / Tulshian, D. / Tata, J. / Fischmann, T.O. / Sondey, C. / Bian, H. / Bober, L. / Jackson, J. / Garlisi, C.G. / ...Authors: McElroy, W.T. / Tan, Z. / Ho, G. / Paliwal, S. / Li, G. / Seganish, W.M. / Tulshian, D. / Tata, J. / Fischmann, T.O. / Sondey, C. / Bian, H. / Bober, L. / Jackson, J. / Garlisi, C.G. / Devito, K. / Fossetta, J. / Lundell, D. / Niu, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4yp8.cif.gz | 237.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4yp8.ent.gz | 191.7 KB | Display | PDB format |
PDBx/mmJSON format | 4yp8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4yp8_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 4yp8_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 4yp8_validation.xml.gz | 43.6 KB | Display | |
Data in CIF | 4yp8_validation.cif.gz | 57.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yp/4yp8 ftp://data.pdbj.org/pub/pdb/validation_reports/yp/4yp8 | HTTPS FTP |
-Related structure data
Related structure data | 4yo6C 2nruS 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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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 33956.195 Da / Num. of mol.: 4 / Fragment: UNP residues 160-460 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / Strain (production host): SF21 References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase #2: Chemical | ChemComp-4GF / #3: Water | ChemComp-HOH / | Has protein modification | 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: 2.65 Å3/Da / Density % sol: 53.57 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, hanging drop / pH: 6.4 Details: 1.80 to 2.0 M Sodium Malonate, 0.2 M Sodium Acetate, 25 mM Hexamminecobalt(III)chloride, 0.05%w/v Pluronic-F-68 PH range: 6.4 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 16, 2011 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.641→47.272 Å / Num. all: 41137 / Num. obs: 41137 / % possible obs: 99 % / Redundancy: 3.3 % / Biso Wilson estimate: 74.06 Å2 / Rpim(I) all: 0.045 / Rrim(I) all: 0.084 / Rsym value: 0.062 / Net I/av σ(I): 6.421 / Net I/σ(I): 11.3 / Num. measured all: 136754 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2NRU Resolution: 2.641→47.27 Å / Cor.coef. Fo:Fc: 0.9292 / Cor.coef. Fo:Fc free: 0.9219 / SU R Cruickshank DPI: 0.73 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.607 / SU Rfree Blow DPI: 0.263 / SU Rfree Cruickshank DPI: 0.273
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Displacement parameters | Biso max: 171.47 Å2 / Biso mean: 72.36 Å2 / Biso min: 25.94 Å2
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Refine analyze | Luzzati coordinate error obs: 0.349 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.641→47.27 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.64→2.71 Å / Total num. of bins used: 20
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