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Yorodumi- PDB-4gb9: Potent and Highly Selective Benzimidazole Inhibitors of PI3K-delta -
+Open data
-Basic information
Entry | Database: PDB / ID: 4gb9 | ||||||
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Title | Potent and Highly Selective Benzimidazole Inhibitors of PI3K-delta | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | ||||||
Keywords | transferase/transferase inhibitor / kinase p110 gamma-isoform / kinase / lipid kinase / transferase-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 / 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 / Synthesis of PIPs at the plasma membrane / regulation of cell adhesion mediated by integrin / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / regulation of angiogenesis / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / T cell activation / neutrophil chemotaxis / ephrin receptor binding / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration / phosphorylation / positive regulation of MAP kinase activity / positive regulation of cytokine production / platelet aggregation / G beta:gamma signalling through PI3Kgamma / endocytosis / kinase activity / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / protein serine kinase activity / innate immune response / protein serine/threonine kinase activity / ATP binding / identical protein binding / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.438 Å | ||||||
Authors | Murray, J.M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Potent and highly selective benzimidazole inhibitors of PI3-kinase delta. Authors: Murray, J.M. / Sweeney, Z.K. / Chan, B.K. / Balazs, M. / Bradley, E. / Castanedo, G. / Chabot, C. / Chantry, D. / Flagella, M. / Goldstein, D.M. / Kondru, R. / Lesnick, J. / Li, J. / Lucas, ...Authors: Murray, J.M. / Sweeney, Z.K. / Chan, B.K. / Balazs, M. / Bradley, E. / Castanedo, G. / Chabot, C. / Chantry, D. / Flagella, M. / Goldstein, D.M. / Kondru, R. / Lesnick, J. / Li, J. / Lucas, M.C. / Nonomiya, J. / Pang, J. / Price, S. / Salphati, L. / Safina, B. / Savy, P.P. / Seward, E.M. / Ultsch, M. / Sutherlin, D.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4gb9.cif.gz | 360.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4gb9.ent.gz | 291.2 KB | Display | PDB format |
PDBx/mmJSON format | 4gb9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gb/4gb9 ftp://data.pdbj.org/pub/pdb/validation_reports/gb/4gb9 | HTTPS FTP |
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-Related structure data
Related structure data | 3tl5S 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: 110727.102 Da / Num. of mol.: 1 / Fragment: unp residues 144-1102 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG / Cell line (production host): Sf9 / 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-0WR / |
#3: 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: 2.1 Å3/Da / Density % sol: 41.53 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: PEG 3350, 0.2M NH4SO4, 0.1M Tris-HCl, pH 8.5, vapor diffusion, hanging drop, temperature 289K |
-Data collection
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
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Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Aug 26, 2009 |
Radiation | Protocol: SINGLE / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→60.93 Å / Num. all: 33625 / Num. obs: 33598 / % possible obs: 97.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.6 % / Biso Wilson estimate: 44 Å2 / Rmerge(I) obs: 0.059 / Net I/σ(I): 14.8 |
Reflection shell | Resolution: 2.43→2.44 Å / Redundancy: 3 % / Rmerge(I) obs: 0.581 / Mean I/σ(I) obs: 3 / Num. unique all: 295 / % possible all: 89.1 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3TL5 Resolution: 2.438→53.654 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.31 / Cross valid method: Random / σ(F): 1.34 / Phase error: 26.5 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 213.9 Å2 / Biso mean: 60.0784 Å2 / Biso min: 19.04 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.438→53.654 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: 12
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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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