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Yorodumi- PDB-4l23: Crystal Structure of p110alpha complexed with niSH2 of p85alpha a... -
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-Basic information
Entry | Database: PDB / ID: 4l23 | ||||||
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Title | Crystal Structure of p110alpha complexed with niSH2 of p85alpha and PI-103 | ||||||
Components | (Phosphatidylinositol ...) x 2 | ||||||
Keywords | signaling Protein/transferase/Inhibitor / ATP binding / PI-103 / signaling Protein-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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.501 Å | ||||||
Authors | Zhang, J. / Zhao, Y.L. / Chen, Y.Y. / Huang, M. / Jiang, F. | ||||||
Citation | Journal: ACS Med Chem Lett / Year: 2014 Title: Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design. Authors: Zhao, Y. / Zhang, X. / Chen, Y. / Lu, S. / Peng, Y. / Wang, X. / Guo, C. / Zhou, A. / Zhang, J. / Luo, Y. / Shen, Q. / Ding, J. / Meng, L. / Zhang, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4l23.cif.gz | 283.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4l23.ent.gz | 223.4 KB | Display | PDB format |
PDBx/mmJSON format | 4l23.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l2/4l23 ftp://data.pdbj.org/pub/pdb/validation_reports/l2/4l23 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Phosphatidylinositol ... , 2 types, 2 molecules AB
#1: Protein | Mass: 124445.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CA / Plasmid: pFastBac HTB / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF9 References: UniProt: P42336, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase |
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#2: Protein | Mass: 39051.469 Da / Num. of mol.: 1 / Fragment: niSH2 of p85alpha, UNP residues 318-615 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GRB1, PIK3R1 / Plasmid: pFastBac HTB / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF9 / References: UniProt: P27986 |
-Non-polymers , 4 types, 256 molecules
#3: Chemical | ChemComp-X6K / | ||||
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#4: Chemical | #5: Chemical | ChemComp-GOL / | #6: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.26 Å3/Da / Density % sol: 45.64 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: 0.15 M Lithium sulfate, 0.1 M Tris PH 8.5, 30%(W/V) PEG 1000MME, vapor diffusion, hanging drop, temperature 291K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.9786 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 13, 2011 |
Radiation | Monochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9786 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→50 Å / Num. all: 51267 / Num. obs: 51267 / % possible obs: 98.3 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 6.7 % / Rmerge(I) obs: 0.077 / Rsym value: 0.077 / Net I/σ(I): 21.7 |
Reflection shell | Resolution: 2.5→2.59 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.505 / Mean I/σ(I) obs: 2.4 / Num. unique all: 4445 / Rsym value: 0.505 / % possible all: 86.7 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.501→38.978 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.32 / σ(F): 0 / Phase error: 28.04 / Stereochemistry target values: ML
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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 max: 120.67 Å2 / Biso mean: 52.6073 Å2 / Biso min: 21.22 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.501→38.978 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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