+Open data
-Basic information
Entry | Database: PDB / ID: 7r9v | ||||||
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Title | Structure of PIK3CA with covalent inhibitor 19 | ||||||
Components | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / PI3K / p110 / PIK3CA / PIP3 / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K ...response to muscle inactivity / negative regulation of actin filament depolymerization / response to L-leucine / regulation of actin filament organization / response to butyrate / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / PI3K events in ERBB4 signaling / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / vasculature development / regulation of cellular respiration / Signaling by cytosolic FGFR1 fusion mutants / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / Nephrin family interactions / anoikis / relaxation of cardiac muscle / Signaling by LTK in cancer / Costimulation by the CD28 family / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / Signaling by LTK / MET activates PI3K/AKT signaling / phosphatidylinositol-4,5-bisphosphate 3-kinase / PI3K/AKT activation / phosphatidylinositol 3-kinase / vascular endothelial growth factor signaling pathway / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / negative regulation of macroautophagy / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / protein kinase activator activity / PI-3K cascade:FGFR4 / response to dexamethasone / PI-3K cascade:FGFR1 / phosphatidylinositol-mediated signaling / Synthesis of PIPs at the plasma membrane / CD28 dependent PI3K/Akt signaling / phosphatidylinositol phosphate biosynthetic process / PI3K events in ERBB2 signaling / PI3K Cascade / negative regulation of anoikis / intercalated disc / RET signaling / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / regulation of multicellular organism growth / positive regulation of TOR signaling / endothelial cell migration / RAC2 GTPase cycle / GAB1 signalosome / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / adipose tissue development / Interleukin receptor SHC signaling / positive regulation of lamellipodium assembly / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / phagocytosis / Signaling by FGFR4 in disease / phosphorylation / cardiac muscle contraction / energy homeostasis / Signaling by FLT3 ITD and TKD mutants / Signaling by FGFR2 in disease / Signaling by FGFR3 in disease / Tie2 Signaling / GPVI-mediated activation cascade / T cell costimulation / FLT3 Signaling / response to muscle stretch / Signaling by FLT3 fusion proteins / RAC1 GTPase cycle / Signaling by FGFR1 in disease / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Downstream signal transduction / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / liver development / insulin-like growth factor receptor signaling pathway / response to activity / Regulation of signaling by CBL / cellular response to glucose stimulus / positive regulation of smooth muscle cell proliferation / regulation of protein phosphorylation / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by SCF-KIT / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / platelet activation / VEGFA-VEGFR2 Pathway Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.69 Å | ||||||
Authors | Burke, J.E. / McPhail, J.A. | ||||||
Funding support | Canada, 1items
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Citation | Journal: J.Am.Chem.Soc. / Year: 2022 Title: Covalent Proximity Scanning of a Distal Cysteine to Target PI3K alpha. Authors: Borsari, C. / Keles, E. / McPhail, J.A. / Schaefer, A. / Sriramaratnam, R. / Goch, W. / Schaefer, T. / De Pascale, M. / Bal, W. / Gstaiger, M. / Burke, J.E. / Wymann, M.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7r9v.cif.gz | 423.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7r9v.ent.gz | 286.3 KB | Display | PDB format |
PDBx/mmJSON format | 7r9v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7r9v_validation.pdf.gz | 718.2 KB | Display | wwPDB validaton report |
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Full document | 7r9v_full_validation.pdf.gz | 737.5 KB | Display | |
Data in XML | 7r9v_validation.xml.gz | 32 KB | Display | |
Data in CIF | 7r9v_validation.cif.gz | 43 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r9/7r9v ftp://data.pdbj.org/pub/pdb/validation_reports/r9/7r9v | HTTPS FTP |
-Related structure data
Related structure data | 7r9yC 4tuuS 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: 110199.398 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CA / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P42336, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-2Q7 / |
Has ligand of interest | Y |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.61 Å3/Da / Density % sol: 52.83 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: PEG6000 8%, 0.6 M sodium formate, 0.1 M CHES pH 9.4, 5 mM TCEP PH range: 9.1-9.7 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9786 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 17, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9786 Å / Relative weight: 1 |
Reflection | Resolution: 2.69→49.26 Å / Num. obs: 32779 / % possible obs: 99.68 % / Redundancy: 6.5 % / Biso Wilson estimate: 89.03 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.06991 / Rpim(I) all: 0.02972 / Rrim(I) all: 0.07611 / Net I/σ(I): 16.49 |
Reflection shell | Resolution: 2.69→2.786 Å / Redundancy: 6.4 % / Rmerge(I) obs: 2.373 / Mean I/σ(I) obs: 0.96 / Num. unique obs: 3221 / CC1/2: 0.465 / CC star: 0.797 / Rpim(I) all: 1.01 / % possible all: 99.47 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4TUU Resolution: 2.69→49.26 Å / SU ML: 0.5608 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 37.2563 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 114.06 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.69→49.26 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A
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