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Yorodumi- PDB-6c1s: Phosphoinositide 3-Kinase gamma bound to an pyrrolopyridinone Inh... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6c1s | ||||||
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Title | Phosphoinositide 3-Kinase gamma bound to an pyrrolopyridinone Inhibitor | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | ||||||
Keywords | Transferase/Transferase Inhibitor / kinase / inhibitor / 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 / FOURIER SYNTHESIS / Resolution: 2.31 Å | ||||||
Authors | Jacobs, M.D. / Griffin, J.P. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase gamma (PI3K gamma ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS). Authors: Come, J.H. / Collier, P.N. / Henderson, J.A. / Pierce, A.C. / Davies, R.J. / Le Tiran, A. / O'Dowd, H. / Bandarage, U.K. / Cao, J. / Deininger, D. / Grey, R. / Krueger, E.B. / Lowe, D.B. / ...Authors: Come, J.H. / Collier, P.N. / Henderson, J.A. / Pierce, A.C. / Davies, R.J. / Le Tiran, A. / O'Dowd, H. / Bandarage, U.K. / Cao, J. / Deininger, D. / Grey, R. / Krueger, E.B. / Lowe, D.B. / Liang, J. / Liao, Y. / Messersmith, D. / Nanthakumar, S. / Sizensky, E. / Wang, J. / Xu, J. / Chin, E.Y. / Damagnez, V. / Doran, J.D. / Dworakowski, W. / Griffith, J.P. / Jacobs, M.D. / Khare-Pandit, S. / Mahajan, S. / Moody, C.S. / Aronov, A.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6c1s.cif.gz | 363.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6c1s.ent.gz | 293.7 KB | Display | PDB format |
PDBx/mmJSON format | 6c1s.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c1/6c1s ftp://data.pdbj.org/pub/pdb/validation_reports/c1/6c1s | HTTPS FTP |
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-Related structure data
Related structure data | 4wwoS 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: 111268.758 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CG / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): sf9 References: UniProt: P48736, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase | ||
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#2: Chemical | ChemComp-EFV / { | ||
#3: Chemical | ChemComp-SO4 / #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: 2.35 Å3/Da / Density % sol: 47.69 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 25% PEG3350, 200MM Lithium Sulfate, 10 MM DTT, 10 MM EDTA, 100 MM Tris |
-Data collection
Diffraction | Mean temperature: 110 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Nov 11, 2009 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.49→62.63 Å / Num. obs: 90461 / % possible obs: 54.2 % / Redundancy: 2.7 % / Biso Wilson estimate: 66.98 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.096 / Rpim(I) all: 0.064 / Rrim(I) all: 0.116 / Net I/σ(I): 4.1 / Num. measured all: 243828 / Scaling rejects: 0 |
Reflection shell | Resolution: 1.49→1.58 Å / Redundancy: 1.6 % / Num. unique obs: 1683 / % possible all: 7 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4wwo Resolution: 2.31→41.12 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.92 / SU R Cruickshank DPI: 0.538 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.505 / SU Rfree Blow DPI: 0.29 / SU Rfree Cruickshank DPI: 0.297
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Displacement parameters | Biso max: 218.78 Å2 / Biso mean: 87.57 Å2 / Biso min: 35.61 Å2
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Refine analyze | Luzzati coordinate error obs: 0.34 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.31→41.12 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.31→2.38 Å / Rfactor Rfree error: 0 / Total num. of bins used: 17
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Refinement TLS params. | Method: refined / Origin x: 35.0899 Å / Origin y: 47.2102 Å / Origin z: 27.5997 Å
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Refinement TLS group | Selection details: { A|144 - A|1090 } |