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Yorodumi- PDB-5eds: Crystal structure of human PI3K-gamma in complex with benzimidazo... -
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-Basic information
Entry | Database: PDB / ID: 5eds | ||||||
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Title | Crystal structure of human PI3K-gamma in complex with benzimidazole inhibitor 5 | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | ||||||
Keywords | Transferase/Transferase Inhibitor / Inhibitor / phosphotransferase / p110 / 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 / regulation of cell adhesion mediated by integrin / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / 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 / phosphatidylinositol 3-kinase/protein kinase B signal transduction / neutrophil chemotaxis / 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 / innate immune response / protein serine kinase activity / 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 / Resolution: 2.8 Å | ||||||
Authors | Whittington, D.A. / Tang, J. / Yakowec, P. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery, Optimization, and in Vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3K delta Inhibitors. Authors: Shin, Y. / Suchomel, J. / Cardozo, M. / Duquette, J. / He, X. / Henne, K. / Hu, Y.L. / Kelly, R.C. / McCarter, J. / McGee, L.R. / Medina, J.C. / Metz, D. / San Miguel, T. / Mohn, D. / Tran, ...Authors: Shin, Y. / Suchomel, J. / Cardozo, M. / Duquette, J. / He, X. / Henne, K. / Hu, Y.L. / Kelly, R.C. / McCarter, J. / McGee, L.R. / Medina, J.C. / Metz, D. / San Miguel, T. / Mohn, D. / Tran, T. / Vissinga, C. / Wong, S. / Wannberg, S. / Whittington, D.A. / Whoriskey, J. / Yu, G. / Zalameda, L. / Zhang, X. / Cushing, T.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5eds.cif.gz | 354.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5eds.ent.gz | 286.3 KB | Display | PDB format |
PDBx/mmJSON format | 5eds.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5eds_validation.pdf.gz | 808.7 KB | Display | wwPDB validaton report |
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Full document | 5eds_full_validation.pdf.gz | 822 KB | Display | |
Data in XML | 5eds_validation.xml.gz | 30.4 KB | Display | |
Data in CIF | 5eds_validation.cif.gz | 42 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ed/5eds ftp://data.pdbj.org/pub/pdb/validation_reports/ed/5eds | HTTPS FTP |
-Related structure data
Related structure data | 4wwpS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
#1: Protein | Mass: 109767.000 Da / Num. of mol.: 1 / Fragment: UNP residues 144-1102 Source method: isolated from a genetically manipulated source Details: catalytic domain / 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 | #3: Chemical | ChemComp-5MT / | #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: 2.38 Å3/Da / Density % sol: 48.35 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.3 Details: 20% PEG 3350, 0.1 M Tris (pH 7.3), 0.25 M ammonium sulfate, 2 mM DTT Temp details: 20 C |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9793 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Sep 26, 2009 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.8→50 Å / Num. obs: 25882 / % possible obs: 99.2 % / Observed criterion σ(I): -3 / Redundancy: 3.3 % / Biso Wilson estimate: 84.3 Å2 / Rmerge(I) obs: 0.07 / Χ2: 1.109 / Net I/av σ(I): 17.562 / Net I/σ(I): 12.9 / Num. measured all: 85045 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 4WWP Resolution: 2.8→40 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.914 / WRfactor Rfree: 0.2887 / WRfactor Rwork: 0.2192 / FOM work R set: 0.7973 / SU B: 35.018 / SU ML: 0.32 / SU R Cruickshank DPI: 0.3248 / SU Rfree: 0.4193 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.419 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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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: 177.58 Å2 / Biso mean: 73.5 Å2 / Biso min: 40.74 Å2
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Refinement step | Cycle: final / Resolution: 2.8→40 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.8→2.872 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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