+Open data
-Basic information
Entry | Database: PDB / ID: 8ucc | ||||||
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Title | IRAK4 in complex with compound 20 | ||||||
Components | (Interleukin-1 receptor-associated kinase 4) x 2 | ||||||
Keywords | TRANSFERASE/INHIBITOR / kinase / 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: 1.8 Å | ||||||
Authors | Metrick, C.M. / Chodaparambil, J.V. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: The Discovery of 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)- N -(6-methylpyrazolo[1,5- a ]pyrimidin-3-yl)imidazo[1,2- a ]pyrimidine-6-carboxamide (BIO-7488), a Potent, Selective, ...Title: The Discovery of 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)- N -(6-methylpyrazolo[1,5- a ]pyrimidin-3-yl)imidazo[1,2- a ]pyrimidine-6-carboxamide (BIO-7488), a Potent, Selective, and CNS-Penetrant IRAK4 Inhibitor for the Treatment of Ischemic Stroke. Authors: Evans, R. / Bolduc, P.N. / Pfaffenbach, M. / Gao, F. / May-Dracka, T. / Fang, T. / Hopkins, B.T. / Chodaparambil, J.V. / Henry, K.L. / Li, P. / Metrick, C. / Nelson, A. / Trapa, P. / Thomas, ...Authors: Evans, R. / Bolduc, P.N. / Pfaffenbach, M. / Gao, F. / May-Dracka, T. / Fang, T. / Hopkins, B.T. / Chodaparambil, J.V. / Henry, K.L. / Li, P. / Metrick, C. / Nelson, A. / Trapa, P. / Thomas, A. / Burkly, L. / Peterson, E.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ucc.cif.gz | 133 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ucc.ent.gz | 98.9 KB | Display | PDB format |
PDBx/mmJSON format | 8ucc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ucc_validation.pdf.gz | 924.9 KB | Display | wwPDB validaton report |
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Full document | 8ucc_full_validation.pdf.gz | 929.2 KB | Display | |
Data in XML | 8ucc_validation.xml.gz | 24.4 KB | Display | |
Data in CIF | 8ucc_validation.cif.gz | 34.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uc/8ucc ftp://data.pdbj.org/pub/pdb/validation_reports/uc/8ucc | HTTPS FTP |
-Related structure data
Related structure data | 8ucbC 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: 34577.961 Da / Num. of mol.: 1 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase | ||||
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#2: Protein | Mass: 34497.980 Da / Num. of mol.: 1 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IRAK4 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q9NWZ3, non-specific serine/threonine protein kinase | ||||
#3: Chemical | Mass: 447.490 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H25N7O3 / Feature type: SUBJECT OF INVESTIGATION #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.8 Å3/Da / Density % sol: 56.08 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / Details: sodium malonate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 1M / Detector: PIXEL / Date: Jul 17, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→90.24 Å / Num. obs: 68053 / % possible obs: 99.9 % / Redundancy: 6.6 % / Biso Wilson estimate: 32.06 Å2 / CC1/2: 0.99 / Net I/σ(I): 16.7 |
Reflection shell | Resolution: 1.8→1.84 Å / Num. unique obs: 3993 / CC1/2: 0.686 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.8→31.99 Å / SU ML: 0.2653 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.3449 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 42.78 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.8→31.99 Å
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Refine LS restraints |
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LS refinement shell |
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