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Yorodumi- PDB-3ibe: Crystal Structure of a Pyrazolopyrimidine Inhibitor Bound to PI3 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3ibe | ||||||
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Title | Crystal Structure of a Pyrazolopyrimidine Inhibitor Bound to PI3 Kinase Gamma | ||||||
Components | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | ||||||
Keywords | TRANSFERASE / PI3Kinase Inhibitor / ATP-binding / Kinase / Nucleotide-binding | ||||||
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 / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis ...secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / T cell chemotaxis / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / sphingosine-1-phosphate receptor signaling pathway / phosphatidylinositol 3-kinase complex, class IA / dendritic cell chemotaxis / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / hepatocyte apoptotic process / positive regulation of Rac protein signal transduction / 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 / positive regulation of endothelial cell migration / neutrophil chemotaxis / 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 / inflammatory response / immune 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: 2.798 Å | ||||||
Authors | Bard, J. / Svenson, K. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines. Authors: Zask, A. / Verheijen, J.C. / Curran, K. / Kaplan, J. / Richard, D.J. / Nowak, P. / Malwitz, D.J. / Brooijmans, N. / Bard, J. / Svenson, K. / Lucas, J. / Toral-Barza, L. / Zhang, W.G. / ...Authors: Zask, A. / Verheijen, J.C. / Curran, K. / Kaplan, J. / Richard, D.J. / Nowak, P. / Malwitz, D.J. / Brooijmans, N. / Bard, J. / Svenson, K. / Lucas, J. / Toral-Barza, L. / Zhang, W.G. / Hollander, I. / Gibbons, J.J. / Abraham, R.T. / Ayral-Kaloustian, S. / Mansour, T.S. / Yu, K. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3ibe.cif.gz | 186.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3ibe.ent.gz | 140.8 KB | Display | PDB format |
PDBx/mmJSON format | 3ibe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ib/3ibe ftp://data.pdbj.org/pub/pdb/validation_reports/ib/3ibe | HTTPS FTP |
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-Related structure data
Related structure data | 1e8yS S: Starting model for refinement |
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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: 110756.164 Da / Num. of mol.: 1 / Fragment: PI3 Kinase Gamma (UNP residues 144 to 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 |
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#2: Chemical | ChemComp-SO4 / |
#3: Chemical | ChemComp-L64 / |
#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: 2.39 Å3/Da / Density % sol: 48.52 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.3 Details: 100 mM Tris pH 8.3, 100 mM Ammonium Sulfate, 17% PEG 3350, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 18, 2006 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.8→50 Å / Num. obs: 23209 / % possible obs: 89.1 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.084 / Χ2: 1.111 / Net I/σ(I): 11.9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1E8Y Resolution: 2.798→44.711 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.727 / SU ML: 0.41 / σ(F): 0.15 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 55.206 Å2 / ksol: 0.288 e/Å3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 158.2 Å2 / Biso mean: 70.848 Å2 / Biso min: 24.54 Å2
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Refinement step | Cycle: LAST / Resolution: 2.798→44.711 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 8
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