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Yorodumi- PDB-4fhj: Crystal Structure of PI3K-gamma in Complex with Imidazopyridine 2 -
+Open data
-Basic information
Entry | Database: PDB / ID: 4fhj | ||||||
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Title | Crystal Structure of PI3K-gamma in Complex with Imidazopyridine 2 | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | ||||||
Keywords | Transferase/Inhibitor / inhibitor / p110 / kinase / transferase / ATP-binding / p84 / p101 / Transferase-Inhibitor complex | ||||||
Function / homology | Function and homology information secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / regulation of calcium ion transmembrane transport / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / T cell chemotaxis ...secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / regulation of calcium ion transmembrane transport / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / T cell chemotaxis / phosphatidylinositol 3-kinase complex, class IB / negative regulation of fibroblast apoptotic process / sphingosine-1-phosphate receptor signaling pathway / dendritic cell chemotaxis / 1-phosphatidylinositol-4-phosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol 3-kinase / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / positive regulation of Rac protein signal transduction / hepatocyte apoptotic process / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / regulation of cell adhesion mediated by integrin / Synthesis of PIPs at the plasma membrane / regulation of angiogenesis / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / T cell activation / ephrin receptor binding / neutrophil chemotaxis / positive regulation of endothelial cell migration / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of cytokine production / positive regulation of MAP kinase activity / platelet aggregation / endocytosis / G beta:gamma signalling through PI3Kgamma / Signaling by CSF1 (M-CSF) in myeloid cells / kinase activity / positive regulation of cytosolic calcium ion concentration / angiogenesis / adaptive immune response / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / protein kinase activity / immune response / inflammatory response / G protein-coupled receptor signaling pathway / phosphorylation / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / ATP binding / membrane / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å | ||||||
Authors | Shaffer, P.L. / Tang, J. / Yakowec, P. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2012 Title: Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors. Authors: Peterson, E.A. / Boezio, A.A. / Andrews, P.S. / Boezio, C.M. / Bush, T.L. / Cheng, A.C. / Choquette, D. / Coats, J.R. / Colletti, A.E. / Copeland, K.W. / Dupont, M. / Graceffa, R. / ...Authors: Peterson, E.A. / Boezio, A.A. / Andrews, P.S. / Boezio, C.M. / Bush, T.L. / Cheng, A.C. / Choquette, D. / Coats, J.R. / Colletti, A.E. / Copeland, K.W. / Dupont, M. / Graceffa, R. / Grubinska, B. / Kim, J.L. / Lewis, R.T. / Liu, J. / Mullady, E.L. / Potashman, M.H. / Romero, K. / Shaffer, P.L. / Stanton, M.K. / Stellwagen, J.C. / Teffera, Y. / Yi, S. / Cai, T. / La, D.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4fhj.cif.gz | 346.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4fhj.ent.gz | 279.4 KB | Display | PDB format |
PDBx/mmJSON format | 4fhj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fh/4fhj ftp://data.pdbj.org/pub/pdb/validation_reports/fh/4fhj | HTTPS FTP |
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-Related structure data
Related structure data | 4fhkC 3qaqS 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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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 109824.055 Da / Num. of mol.: 1 / Fragment: catalytic domain (UNP residues 144-1102) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase | ||||
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#2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-0TZ / | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.32 Å3/Da / Density % sol: 46.96 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.8 Details: 19.6% PEG 3350, 0.1M Tris, 0.1M ammonium sulfate, 10 mM DTT, pH 7.8, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 8, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.6→50 Å / Num. obs: 31165 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 3.7 % / Rmerge(I) obs: 0.071 / Χ2: 1.036 / Net I/σ(I): 11.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB Entry 3QAQ Resolution: 2.6→44.58 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.921 / Occupancy max: 1 / Occupancy min: 1 / SU B: 25.952 / SU ML: 0.264 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.784 / ESU R Free: 0.316 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 154.15 Å2 / Biso mean: 72.2468 Å2 / Biso min: 31.82 Å2
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Refinement step | Cycle: LAST / Resolution: 2.6→44.58 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.6→2.666 Å / Total num. of bins used: 20
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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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