+Open data
-Basic information
Entry | Database: PDB / ID: 5t8f | ||||||
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Title | p110delta/p85alpha with taselisib (GDC-0032) | ||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / PI3KDELTA KINASE / PROTEROS BIOSTRUCTURES GMBH / inhibitor / lipid kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information mast cell differentiation / mast cell chemotaxis / B cell chemotaxis / RHOC GTPase cycle / PI3K events in ERBB4 signaling / Interleukin-7 signaling / GAB1 signalosome / PI3K events in ERBB2 signaling / MET activates PI3K/AKT signaling / CDC42 GTPase cycle ...mast cell differentiation / mast cell chemotaxis / B cell chemotaxis / RHOC GTPase cycle / PI3K events in ERBB4 signaling / Interleukin-7 signaling / GAB1 signalosome / PI3K events in ERBB2 signaling / MET activates PI3K/AKT signaling / CDC42 GTPase cycle / RHOD GTPase cycle / RHOJ GTPase cycle / RAC3 GTPase cycle / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / FLT3 Signaling / RND2 GTPase cycle / RND1 GTPase cycle / IRS-mediated signalling / GPVI-mediated activation cascade / Signaling by SCF-KIT / Downstream signal transduction / PI3K/AKT activation / Signaling by ALK / Role of phospholipids in phagocytosis / Tie2 Signaling / Role of LAT2/NTAL/LAB on calcium mobilization / Costimulation by the CD28 family / CD28 dependent PI3K/Akt signaling / RAC1 GTPase cycle / RAC2 GTPase cycle / Interleukin receptor SHC signaling / RND3 GTPase cycle / PI-3K cascade:FGFR1 / PI-3K cascade:FGFR2 / PI-3K cascade:FGFR3 / PI-3K cascade:FGFR4 / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / PI3K Cascade / PIP3 activates AKT signaling / GP1b-IX-V activation signalling / RAF/MAP kinase cascade / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Synthesis of PIPs at the plasma membrane / RHOA GTPase cycle / RHOF GTPase cycle / DAP12 signaling / RHOU GTPase cycle / RHOV GTPase cycle / Regulation of signaling by CBL / Downstream TCR signaling / natural killer cell differentiation / RHOG GTPase cycle / positive regulation of epithelial tube formation / RET signaling / natural killer cell chemotaxis / Interleukin-3, Interleukin-5 and GM-CSF signaling / neutrophil extravasation / VEGFA-VEGFR2 Pathway / positive regulation of neutrophil apoptotic process / respiratory burst involved in defense response / phosphatidylinositol 3-kinase regulator activity / phosphatidylinositol 3-kinase activator activity / 1-phosphatidylinositol-3-kinase regulator activity / T cell chemotaxis / natural killer cell activation / positive regulation of endoplasmic reticulum unfolded protein response / ErbB-3 class receptor binding / transmembrane receptor protein tyrosine kinase adaptor activity / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / enzyme-substrate adaptor activity / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / Extra-nuclear estrogen signaling / phosphatidylinositol 3-kinase / vascular endothelial growth factor signaling pathway / G alpha (q) signalling events / phosphatidylinositol-3-phosphate biosynthetic process / mast cell degranulation / 1-phosphatidylinositol-3-kinase activity / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / intracellular glucose homeostasis / B cell activation / phosphatidylinositol-mediated signaling / Synthesis of PIPs at the plasma membrane / phosphatidylinositol phosphate biosynthetic process / T cell differentiation / RET signaling / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / phosphorylation / insulin-like growth factor receptor binding / positive regulation of endothelial cell proliferation / response to endoplasmic reticulum stress / neutrophil chemotaxis / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Bos taurus (cattle) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.91 Å | ||||||
Authors | Moertl, M. / Steinbacher, S. / Eigenbrot, C. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2017 Title: Structure-Based Design of Tricyclic NF-kappa B Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K). Authors: Castanedo, G.M. / Blaquiere, N. / Beresini, M. / Bravo, B. / Brightbill, H. / Chen, J. / Cui, H.F. / Eigenbrot, C. / Everett, C. / Feng, J. / Godemann, R. / Gogol, E. / Hymowitz, S. / ...Authors: Castanedo, G.M. / Blaquiere, N. / Beresini, M. / Bravo, B. / Brightbill, H. / Chen, J. / Cui, H.F. / Eigenbrot, C. / Everett, C. / Feng, J. / Godemann, R. / Gogol, E. / Hymowitz, S. / Johnson, A. / Kayagaki, N. / Kohli, P.B. / Knuppel, K. / Kraemer, J. / Kruger, S. / Loke, P. / McEwan, P. / Montalbetti, C. / Roberts, D.A. / Smith, M. / Steinbacher, S. / Sujatha-Bhaskar, S. / Takahashi, R. / Wang, X. / Wu, L.C. / Zhang, Y. / Staben, S.T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5t8f.cif.gz | 446.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5t8f.ent.gz | 362.1 KB | Display | PDB format |
PDBx/mmJSON format | 5t8f.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5t8f_validation.pdf.gz | 691.5 KB | Display | wwPDB validaton report |
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Full document | 5t8f_full_validation.pdf.gz | 697.6 KB | Display | |
Data in XML | 5t8f_validation.xml.gz | 36.1 KB | Display | |
Data in CIF | 5t8f_validation.cif.gz | 50.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t8/5t8f ftp://data.pdbj.org/pub/pdb/validation_reports/t8/5t8f | HTTPS FTP |
-Related structure data
Related structure data | 5t8oC 5t8pC 5t8qC 5dxuS S: Starting model for refinement C: citing same article (ref.) |
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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: 116187.164 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3CD / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O00329, phosphatidylinositol-4,5-bisphosphate 3-kinase |
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#2: Protein | Mass: 20879.555 Da / Num. of mol.: 1 / Fragment: PI3-KINASE P110 DELTA AND P85 FRAGMENT Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: PIK3R1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P23727 |
#3: Chemical | ChemComp-799 / |
#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: 2.64 Å3/Da / Density % sol: 53.45 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.99988 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jan 17, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99988 Å / Relative weight: 1 |
Reflection | Resolution: 2.91→86.37 Å / Num. obs: 31603 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 8.1 % / Rsym value: 0.063 / Net I/σ(I): 20.4 |
Reflection shell | Resolution: 2.91→3.16 Å / Redundancy: 8.1 % / Rmerge(I) obs: 0.044 / Mean I/σ(I) obs: 5.6 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5DXU Resolution: 2.91→86.37 Å / Cor.coef. Fo:Fc: 0.924 / Cor.coef. Fo:Fc free: 0.878 / SU B: 50.797 / SU ML: 0.422 / Cross valid method: THROUGHOUT / ESU R Free: 0.468 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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 mean: 77.62 Å2
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Refinement step | Cycle: LAST / Resolution: 2.91→86.37 Å
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Refine LS restraints |
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