+Open data
-Basic information
Entry | Database: PDB / ID: 5sxb | |||||||||
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Title | Crystal Structure of PI3Kalpha in complex with fragment 23 | |||||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / lipid kinase / phosphoinositide / 3-kinase / signaling / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex | |||||||||
Function / homology | Function and homology information perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / autosome genomic imprinting ...perinuclear endoplasmic reticulum membrane / response to muscle inactivity / negative regulation of actin filament depolymerization / regulation of toll-like receptor 4 signaling pathway / response to L-leucine / phosphatidylinositol kinase activity / regulation of actin filament organization / phosphatidylinositol 3-kinase regulator activity / response to butyrate / autosome genomic imprinting / positive regulation of focal adhesion disassembly / cellular response to hydrostatic pressure / IRS-mediated signalling / phosphatidylinositol 3-kinase activator activity / interleukin-18-mediated signaling pathway / PI3K events in ERBB4 signaling / myeloid leukocyte migration / phosphatidylinositol 3-kinase regulatory subunit binding / 1-phosphatidylinositol-3-kinase regulator activity / neurotrophin TRKA receptor binding / Activated NTRK2 signals through PI3K / positive regulation of protein localization to membrane / cis-Golgi network / Activated NTRK3 signals through PI3K / kinase activator activity / ErbB-3 class receptor binding / negative regulation of fibroblast apoptotic process / RHOF GTPase cycle / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOD GTPase cycle / positive regulation of endoplasmic reticulum unfolded protein response / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / enzyme-substrate adaptor activity / phosphatidylinositol 3-kinase complex / anoikis / Nephrin family interactions / 1-phosphatidylinositol-4-phosphate 3-kinase activity / RND1 GTPase cycle / Costimulation by the CD28 family / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / vascular endothelial growth factor signaling pathway / RND2 GTPase cycle / PI3K/AKT activation / MET activates PI3K/AKT signaling / RND3 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / positive regulation of leukocyte migration / positive regulation of filopodium assembly / phosphatidylinositol 3-kinase / phosphatidylinositol 3-kinase complex, class IA / negative regulation of stress fiber assembly / relaxation of cardiac muscle / growth hormone receptor signaling pathway / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / RHOV GTPase cycle / negative regulation of macroautophagy / GP1b-IX-V activation signalling / RHOB GTPase cycle / Signaling by ALK / negative regulation of cell-matrix adhesion / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / protein kinase activator activity / response to dexamethasone / PI-3K cascade:FGFR2 / RHOJ GTPase cycle / PI-3K cascade:FGFR4 / RHOC GTPase cycle / PI-3K cascade:FGFR1 / negative regulation of osteoclast differentiation / intracellular glucose homeostasis / CD28 dependent PI3K/Akt signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol phosphate biosynthetic process / CDC42 GTPase cycle / RHOU GTPase cycle / PI3K events in ERBB2 signaling / Signaling by ALK fusions and activated point mutants / RHOG GTPase cycle / regulation of multicellular organism growth / negative regulation of anoikis / RET signaling / T cell differentiation / extrinsic apoptotic signaling pathway via death domain receptors / insulin receptor substrate binding / PI3K Cascade / Interleukin-3, Interleukin-5 and GM-CSF signaling / RHOA GTPase cycle / intercalated disc / positive regulation of TOR signaling / endothelial cell migration / RAC3 GTPase cycle / RAC2 GTPase cycle / Role of phospholipids in phagocytosis 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 | 5sxb.cif.gz | 278.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5sxb.ent.gz | 218.6 KB | Display | PDB format |
PDBx/mmJSON format | 5sxb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sx/5sxb ftp://data.pdbj.org/pub/pdb/validation_reports/sx/5sxb | HTTPS FTP |
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-Related structure data
Related structure data | 5sw8C 5swgC 5swoC 5swpC 5swrC 5swtC 5sx8C 5sx9C 5sxaC 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: 127982.531 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CA / 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-SOA / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.11 Å3/Da / Density % sol: 60.4 % / Mosaicity: 0.586 ° / Mosaicity esd: 0.007 ° |
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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→92.16 Å / Num. obs: 31023 / % possible obs: 100 % / Redundancy: 7.3 % / Rmerge(I) obs: 0.107 / Net I/av σ(I): 23.706 / Net I/σ(I): 8.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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→92.16 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.882 / SU B: 25.26 / SU ML: 0.412 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.56 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: 278.51 Å2 / Biso mean: 120.088 Å2 / Biso min: 45.24 Å2
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Refinement step | Cycle: final / Resolution: 3.3→92.16 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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