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Yorodumi- PDB-5sw8: Crystal structure of PI3Kalpha in complex with fragments 7 and 11 -
+Open data
-Basic information
Entry | Database: PDB / ID: 5sw8 | |||||||||
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Title | Crystal structure of PI3Kalpha in complex with fragments 7 and 11 | |||||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / lipid kinase / phosphoinositide / 3-kinase / signaling / TRANSFERASE-TRANSFERASE INHIBITOR complex | |||||||||
Function / homology | Function and homology information perinuclear endoplasmic reticulum membrane / response to muscle inactivity / regulation of toll-like receptor 4 signaling pathway / negative regulation of actin filament depolymerization / phosphatidylinositol kinase activity / response to L-leucine / regulation of actin filament organization / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling ...perinuclear endoplasmic reticulum membrane / response to muscle inactivity / regulation of toll-like receptor 4 signaling pathway / negative regulation of actin filament depolymerization / phosphatidylinositol kinase activity / response to L-leucine / regulation of actin filament organization / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling / positive regulation of focal adhesion disassembly / cellular response to hydrostatic pressure / phosphatidylinositol 3-kinase activator activity / autosome genomic imprinting / interleukin-18-mediated signaling pathway / PI3K events in ERBB4 signaling / myeloid leukocyte migration / 1-phosphatidylinositol-3-kinase regulator activity / phosphatidylinositol 3-kinase regulatory subunit binding / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / positive regulation of endoplasmic reticulum unfolded protein response / positive regulation of protein localization to membrane / Activated NTRK3 signals through PI3K / negative regulation of fibroblast apoptotic process / cis-Golgi network / ErbB-3 class receptor binding / kinase activator activity / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / regulation of cellular respiration / RHOF GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / RHOD GTPase cycle / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / enzyme-substrate adaptor activity / Nephrin family interactions / anoikis / Signaling by LTK in cancer / Costimulation by the CD28 family / RND1 GTPase cycle / Signaling by LTK / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / relaxation of cardiac muscle / MET activates PI3K/AKT signaling / positive regulation of leukocyte migration / PI3K/AKT activation / RND2 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / positive regulation of filopodium assembly / RND3 GTPase cycle / growth hormone receptor signaling pathway / vascular endothelial growth factor signaling pathway / phosphatidylinositol 3-kinase / negative regulation of stress fiber assembly / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / natural killer cell mediated cytotoxicity / 1-phosphatidylinositol-3-kinase activity / RHOV GTPase cycle / negative regulation of cell-matrix adhesion / Signaling by ALK / negative regulation of macroautophagy / RHOB GTPase cycle / GP1b-IX-V activation signalling / 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 / RHOC GTPase cycle / RHOJ GTPase cycle / negative regulation of osteoclast differentiation / intracellular glucose homeostasis / phosphatidylinositol-mediated signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol phosphate biosynthetic process / CD28 dependent PI3K/Akt signaling / RHOU GTPase cycle / CDC42 GTPase cycle / PI3K events in ERBB2 signaling / negative regulation of anoikis / PI3K Cascade / RET signaling / intercalated disc / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / T cell differentiation / RHOG GTPase cycle / regulation of multicellular organism growth / extrinsic apoptotic signaling pathway via death domain receptors / endothelial cell migration / positive regulation of TOR signaling / RHOA GTPase cycle Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 3.3 Å | |||||||||
Authors | Gabelli, S.B. / Vogelstein, B. / Miller, M.S. / Amzel, L.M. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Bioorg. Med. Chem. / Year: 2017 Title: Identification of allosteric binding sites for PI3K alpha oncogenic mutant specific inhibitor design. Authors: Miller, M.S. / Maheshwari, S. / McRobb, F.M. / Kinzler, K.W. / Amzel, L.M. / Vogelstein, B. / Gabelli, S.B. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5sw8.cif.gz | 274.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5sw8.ent.gz | 213.5 KB | Display | PDB format |
PDBx/mmJSON format | 5sw8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5sw8_validation.pdf.gz | 498.2 KB | Display | wwPDB validaton report |
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Full document | 5sw8_full_validation.pdf.gz | 521.7 KB | Display | |
Data in XML | 5sw8_validation.xml.gz | 43.8 KB | Display | |
Data in CIF | 5sw8_validation.cif.gz | 60 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sw/5sw8 ftp://data.pdbj.org/pub/pdb/validation_reports/sw/5sw8 | HTTPS FTP |
-Related structure data
Related structure data | 5swgC 5swoC 5swpC 5swrC 5swtC 5sx8C 5sx9C 5sxaC 5sxbC 5sxcC 5sxdC 5sxeC 5sxfC 5sxiC 5sxjC 5sxkC 4ovuS C: citing same article (ref.) 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: 127902.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CA / Variant: SF9 / Plasmid: pFastbac HT-A / Cell line (production host): SF9 / 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: Protein | Mass: 33666.961 Da / Num. of mol.: 1 / Fragment: residues 322-600 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3R1, GRB1 / Plasmid: pFastbac HT-A / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27986 |
#3: Chemical | ChemComp-EPE / |
#4: Chemical | ChemComp-70S / |
#5: Chemical |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.22 Å3/Da / Density % sol: 61.77 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: NaFormate |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Oct 17, 2014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 3.3→93.24 Å / Num. obs: 31971 / % possible obs: 99.9 % / Redundancy: 7.1 % / Rmerge(I) obs: 0.101 / Net I/av σ(I): 26.474 / Net I/σ(I): 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4OVU Resolution: 3.3→93.24 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.874 / SU B: 29.963 / SU ML: 0.476 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.586 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 308.09 Å2 / Biso mean: 122.951 Å2 / Biso min: 50.65 Å2
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Refinement step | Cycle: final / Resolution: 3.3→93.24 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.3→3.386 Å / Total num. of bins used: 20
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