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Yorodumi- PDB-4zop: Co-crystal Structure of Lipid Kinase PI3K alpha with a selective ... -
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-Basic information
Entry | Database: PDB / ID: 4zop | ||||||
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Title | Co-crystal Structure of Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitor | ||||||
Components |
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Keywords | transferase/transferase inhibitor / Lipid kinase / 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 / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling ...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 / response to butyrate / phosphatidylinositol 3-kinase regulator activity / IRS-mediated signalling / cellular response to hydrostatic pressure / autosome genomic imprinting / positive regulation of focal adhesion disassembly / phosphatidylinositol 3-kinase activator activity / 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 protein localization to membrane / Activated NTRK3 signals through PI3K / cis-Golgi network / ErbB-3 class receptor binding / negative regulation of fibroblast apoptotic process / kinase activator activity / phosphatidylinositol 3-kinase complex, class IB / vasculature development / transmembrane receptor protein tyrosine kinase adaptor activity / RHOF GTPase cycle / RHOD GTPase cycle / Signaling by cytosolic FGFR1 fusion mutants / regulation of cellular respiration / positive regulation of endoplasmic reticulum unfolded protein response / cardiac muscle cell contraction / phosphatidylinositol 3-kinase complex, class IA / enzyme-substrate adaptor activity / anoikis / phosphatidylinositol 3-kinase complex / Nephrin family interactions / Signaling by LTK in cancer / PI3K events in ERBB2 signaling / RND1 GTPase cycle / relaxation of cardiac muscle / Costimulation by the CD28 family / Signaling by LTK / positive regulation of leukocyte migration / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / MET activates PI3K/AKT signaling / RND2 GTPase cycle / PI3K/AKT activation / positive regulation of filopodium assembly / RND3 GTPase cycle / phosphatidylinositol-4,5-bisphosphate 3-kinase / vascular endothelial growth factor signaling pathway / negative regulation of stress fiber assembly / growth hormone receptor signaling pathway / phosphatidylinositol 3-kinase / natural killer cell mediated cytotoxicity / insulin binding / phosphatidylinositol-3-phosphate biosynthetic process / RHOV GTPase cycle / negative regulation of macroautophagy / 1-phosphatidylinositol-3-kinase activity / Signaling by ALK / negative regulation of cell-matrix adhesion / RHOB GTPase cycle / GP1b-IX-V activation signalling / GAB1 signalosome / PI-3K cascade:FGFR3 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / PI-3K cascade:FGFR2 / protein kinase activator activity / response to dexamethasone / PI-3K cascade:FGFR4 / RHOC GTPase cycle / RHOJ 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-mediated signaling / phosphatidylinositol phosphate biosynthetic process / CDC42 GTPase cycle / RHOU GTPase cycle / negative regulation of anoikis / intercalated disc / RET signaling / T cell differentiation / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / RHOG GTPase cycle / extrinsic apoptotic signaling pathway via death domain receptors / regulation of multicellular organism growth / PI3K Cascade / RHOA GTPase cycle / endothelial cell migration Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.62 Å | ||||||
Authors | Knapp, M.S. / Elling, R.A. | ||||||
Citation | Journal: To Be Published Title: Co-crystal Structure of the Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitorCo-crystal Structure of the Lipid Kinase PI3K alpha with a selective ...Title: Co-crystal Structure of the Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitorCo-crystal Structure of the Lipid Kinase PI3K alpha with a selective phosphatidylinositol-3 kinase alpha inhibitor Authors: Fairhurst, R.A. / Gerspacher, M. / Imbach-Weese, P. / Mah, R. / Caravatti, G. / Fuert, P. / Fritsch, C. / Schnell, C. / Blanz, J. / Blasco, F. / Desrayaud, S. / Guthy, D.A. / Knapp, M.S. / ...Authors: Fairhurst, R.A. / Gerspacher, M. / Imbach-Weese, P. / Mah, R. / Caravatti, G. / Fuert, P. / Fritsch, C. / Schnell, C. / Blanz, J. / Blasco, F. / Desrayaud, S. / Guthy, D.A. / Knapp, M.S. / Arz, D. / Wirth, J. / Roehn-Carnemolla, E. / Luu, V.H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4zop.cif.gz | 520 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4zop.ent.gz | 424.9 KB | Display | PDB format |
PDBx/mmJSON format | 4zop.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4zop_validation.pdf.gz | 737.8 KB | Display | wwPDB validaton report |
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Full document | 4zop_full_validation.pdf.gz | 744.4 KB | Display | |
Data in XML | 4zop_validation.xml.gz | 43 KB | Display | |
Data in CIF | 4zop_validation.cif.gz | 60.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zo/4zop ftp://data.pdbj.org/pub/pdb/validation_reports/zo/4zop | HTTPS FTP |
-Related structure data
Related structure data | 4jpsS 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: 125287.828 Da / Num. of mol.: 1 / Mutation: M232K, L233K 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: Protein | Mass: 34756.258 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3R1, GRB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P27986 |
#3: Chemical | ChemComp-4Q2 / ( |
#4: 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: 2.35 Å3/Da / Density % sol: 47.69 % |
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Crystal grow | Temperature: 303 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 12% PEG 3350, 120MM KSCN, 6UL PROTEIN TO 4UL WELL WITH STREAK SEEDING AT 18C , PH 7.5, VAPOR DIFFUSION, HANGING DROP |
-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: ADSC QUANTUM 315r / Detector: CCD / Date: Jun 4, 2009 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.62→47.49 Å / Num. obs: 46254 / % possible obs: 100 % / Redundancy: 7.4 % / Biso Wilson estimate: 77.21 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.07 / Rpim(I) all: 0.028 / Net I/σ(I): 21 / Num. measured all: 340332 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4JPS Resolution: 2.62→47.49 Å / Cor.coef. Fo:Fc: 0.9429 / Cor.coef. Fo:Fc free: 0.8938 / SU R Cruickshank DPI: 0.709 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.68 / SU Rfree Blow DPI: 0.311 / SU Rfree Cruickshank DPI: 0.317
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Displacement parameters | Biso max: 176.1 Å2 / Biso mean: 68.91 Å2 / Biso min: 30.33 Å2
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Refine analyze | Luzzati coordinate error obs: 0.357 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.62→47.49 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.62→2.69 Å / 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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