+Open data
-Basic information
Entry | Database: PDB / ID: 7r2b | ||||||
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Title | PI3Kdelta in complex with an inhibitor | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform | ||||||
Keywords | HYDROLASE / kinase / complex / inhibitor | ||||||
Function / homology | Function and homology information Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin receptor SHC signaling / Synthesis of PIPs at the plasma membrane / PIP3 activates AKT signaling / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of signaling by CBL / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / RET signaling / phosphatidylinositol 3-kinase complex ...Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin receptor SHC signaling / Synthesis of PIPs at the plasma membrane / PIP3 activates AKT signaling / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of signaling by CBL / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / RET signaling / phosphatidylinositol 3-kinase complex / 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 / B cell activation / phosphatidylinositol-mediated signaling / B cell homeostasis / homeostasis of number of cells / defense response to fungus / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of angiogenesis / chemotaxis / kinase activity / adaptive immune response / cell differentiation / cell surface receptor signaling pathway / inflammatory response / negative regulation of gene expression / innate immune response / positive regulation of gene expression / ATP binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Gutmann, S. / Rummel, G. / Shrestha, B. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Identification of NVP-CLR457 as an Orally Bioavailable Non-CNS-Penetrant pan-Class IA Phosphoinositol-3-Kinase Inhibitor. Authors: Fairhurst, R.A. / Furet, P. / Imbach-Weese, P. / Stauffer, F. / Rueeger, H. / McCarthy, C. / Ripoche, S. / Oswald, S. / Arnaud, B. / Jary, A. / Maira, M. / Schnell, C. / Guthy, D.A. / ...Authors: Fairhurst, R.A. / Furet, P. / Imbach-Weese, P. / Stauffer, F. / Rueeger, H. / McCarthy, C. / Ripoche, S. / Oswald, S. / Arnaud, B. / Jary, A. / Maira, M. / Schnell, C. / Guthy, D.A. / Wartmann, M. / Kiffe, M. / Desrayaud, S. / Blasco, F. / Widmer, T. / Seiler, F. / Gutmann, S. / Knapp, M. / Caravatti, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7r2b.cif.gz | 317.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7r2b.ent.gz | 250.6 KB | Display | PDB format |
PDBx/mmJSON format | 7r2b.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r2/7r2b ftp://data.pdbj.org/pub/pdb/validation_reports/r2/7r2b | HTTPS FTP |
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-Related structure data
Related structure data | 7r26C 7tz7C 5is5S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 107823.664 Da / Num. of mol.: 1 / Fragment: P110 SUBUNIT, UNP RESIDUES 106-1044 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Pik3cd / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O35904, phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase |
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#2: Chemical | ChemComp-H5I / ( |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.41 Å3/Da / Density % sol: 48.99 % |
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Crystal grow | Temperature: 290 K / Method: vapor diffusion, hanging drop Details: 4 mM NaNO4,36mM AS,.9mM Na2HPO4,13.1% glycerol, 9.1% PEG4000, 0.1M imidazole pH6.9 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 6, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.515→114.095 Å / Num. obs: 35003 / % possible obs: 99.3 % / Redundancy: 3.3 % / CC1/2: 0.998 / Rmerge(I) obs: 0.069 / Rpim(I) all: 0.045 / Net I/σ(I): 10.6 |
Reflection shell | Resolution: 2.515→2.558 Å / Redundancy: 2.1 % / Rmerge(I) obs: 0.615 / Mean I/σ(I) obs: 3.3 / Num. unique obs: 1742 / CC1/2: 0.745 / Rpim(I) all: 0.401 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5IS5 Resolution: 2.7→58.14 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.907 / SU R Cruickshank DPI: 0.697 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.664 / SU Rfree Blow DPI: 0.322 / SU Rfree Cruickshank DPI: 0.329
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Displacement parameters | Biso mean: 70.83 Å2
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Refine analyze | Luzzati coordinate error obs: 0.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7→58.14 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.7→2.72 Å
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Refinement TLS params. | Origin x: 18.5075 Å / Origin y: -15.4869 Å / Origin z: -28.2877 Å
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Refinement TLS group | Selection details: { A|* } |