+Open data
-Basic information
Entry | Database: PDB / ID: 7jis | ||||||
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Title | HUMAN PI3KDELTA IN COMPLEX WITH COMPOUND 2F | ||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / PI3KDELTA KINASE / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX | ||||||
Function / homology | Function and homology information B cell chemotaxis / Signaling by ALK / MET activates PI3K/AKT signaling / RHOC GTPase cycle / CDC42 GTPase cycle / RAC1 GTPase cycle / RAC2 GTPase cycle / RHOD GTPase cycle / RHOJ GTPase cycle / RAC3 GTPase cycle ...B cell chemotaxis / Signaling by ALK / MET activates PI3K/AKT signaling / RHOC GTPase cycle / CDC42 GTPase cycle / RAC1 GTPase cycle / RAC2 GTPase cycle / RHOD GTPase cycle / RHOJ GTPase cycle / RAC3 GTPase cycle / FLT3 Signaling / RND3 GTPase cycle / RND2 GTPase cycle / RND1 GTPase cycle / PI3K events in ERBB4 signaling / Interleukin-7 signaling / GAB1 signalosome / PI3K events in ERBB2 signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / IRS-mediated signalling / GPVI-mediated activation cascade / Signaling by SCF-KIT / Downstream signal transduction / PI3K/AKT activation / Role of phospholipids in phagocytosis / Tie2 Signaling / Role of LAT2/NTAL/LAB on calcium mobilization / Costimulation by the CD28 family / CD28 dependent PI3K/Akt signaling / RAF/MAP kinase cascade / Interleukin receptor SHC signaling / PI-3K cascade:FGFR1 / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR3 / PI-3K cascade:FGFR4 / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / PI3K Cascade / PIP3 activates AKT signaling / GP1b-IX-V activation signalling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Synthesis of PIPs at the plasma membrane / RHOA GTPase cycle / RHOF GTPase cycle / DAP12 signaling / RHOU GTPase cycle / RHOV GTPase cycle / mast cell differentiation / mast cell chemotaxis / Regulation of signaling by CBL / Downstream TCR signaling / natural killer cell differentiation / RHOG GTPase cycle / positive regulation of epithelial tube formation / RET signaling / natural killer cell chemotaxis / Interleukin-3, Interleukin-5 and GM-CSF signaling / VEGFA-VEGFR2 Pathway / neutrophil extravasation / positive regulation of neutrophil apoptotic process / respiratory burst involved in defense response / phosphatidylinositol 3-kinase regulator activity / phosphatidylinositol 3-kinase activator activity / 1-phosphatidylinositol-3-kinase regulator activity / T cell chemotaxis / natural killer cell activation / ErbB-3 class receptor binding / transmembrane receptor protein tyrosine kinase adaptor activity / positive regulation of endoplasmic reticulum unfolded protein response / phosphatidylinositol 3-kinase complex, class IA / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / Extra-nuclear estrogen signaling / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / phosphatidylinositol 3-kinase / G alpha (q) signalling events / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / B cell activation / intracellular glucose homeostasis / Synthesis of PIPs at the plasma membrane / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / RET signaling / T cell differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / positive regulation of endothelial cell proliferation / insulin-like growth factor receptor binding / T cell activation / neutrophil chemotaxis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration / phosphorylation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Bos taurus (cattle) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.42 Å | ||||||
Authors | Lesburg, C.A. / Augustin, M. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2020 Title: Optimization of Versatile Oxindoles as Selective PI3K delta Inhibitors. Authors: Methot, J.L. / Achab, A. / Christopher, M. / Zhou, H. / McGowan, M.A. / Trotter, B.W. / Fradera, X. / Lesburg, C.A. / Goldenblatt, P. / Hill, A. / Chen, D. / Otte, K.M. / Augustin, M. / Shah, S. / Katz, J.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7jis.cif.gz | 467.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jis.ent.gz | 378.8 KB | Display | PDB format |
PDBx/mmJSON format | 7jis.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7jis_validation.pdf.gz | 776.8 KB | Display | wwPDB validaton report |
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Full document | 7jis_full_validation.pdf.gz | 785.7 KB | Display | |
Data in XML | 7jis_validation.xml.gz | 37.1 KB | Display | |
Data in CIF | 7jis_validation.cif.gz | 51.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ji/7jis ftp://data.pdbj.org/pub/pdb/validation_reports/ji/7jis | HTTPS FTP |
-Related 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: 116600.633 Da / Num. of mol.: 1 Fragment: PI3-KINASE P110 DELTA AND P85 FRAGMENT, residues 17-1034 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CD / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O00329, phosphatidylinositol-4,5-bisphosphate 3-kinase |
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#2: Protein | Mass: 20879.555 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: PIK3R1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P23727 |
#3: Chemical | ChemComp-VBS / ( |
#4: 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: 2.62 Å3/Da / Density % sol: 53.09 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / Details: 16% PEG6000, 0.10 M KCL, 0.10 M MES pH 6.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 20, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.42→86.17 Å / Num. obs: 53166 / % possible obs: 98.4 % / Redundancy: 4.3 % / Biso Wilson estimate: 72.775 Å2 / CC1/2: 0.997 / Rrim(I) all: 0.062 / Rsym value: 0.054 / Χ2: 1.006 / Net I/σ(I): 14.26 |
Reflection shell | Resolution: 2.42→2.67 Å / Redundancy: 4.3 % / Mean I/σ(I) obs: 3.28 / Num. unique obs: 13527 / CC1/2: 0.991 / Rrim(I) all: 0.637 / Rsym value: 0.561 / % possible all: 99.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: previously determined structure Resolution: 2.42→86.17 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.922 / SU B: 21.095 / SU ML: 0.224 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.389 / ESU R Free: 0.269 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 204.74 Å2 / Biso mean: 77.666 Å2 / Biso min: 35.08 Å2
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Refinement step | Cycle: final / Resolution: 2.42→86.17 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.42→2.483 Å / Rfactor Rfree error: 0 / 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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