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Yorodumi- PDB-3en6: Targeted polypharmacology: crystal structure of the c-Src kinase ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3en6 | ||||||
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Title | Targeted polypharmacology: crystal structure of the c-Src kinase domain in complex with PP102, a multitargeted kinase inhibitor | ||||||
Components | Proto-oncogene tyrosine-protein kinase Src | ||||||
Keywords | TRANSFERASE / SRC / tyrosine / kinase / polypharmacology / inhibitor / multitarget / phosphoinositide / signaling / pyrazolopyrimidine / kinase-inhibitor complex / ATP-binding / Lipoprotein / Myristate / Nucleotide-binding / Phosphoprotein / Proto-oncogene / SH2 domain / SH3 domain / Tyrosine-protein kinase | ||||||
Function / homology | Function and homology information Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions ...Signaling by ERBB2 / Nuclear signaling by ERBB4 / PIP3 activates AKT signaling / Signaling by SCF-KIT / Regulation of KIT signaling / Signaling by EGFR / GAB1 signalosome / Regulation of gap junction activity / FCGR activation / PECAM1 interactions / CD28 co-stimulation / CTLA4 inhibitory signaling / EPHA-mediated growth cone collapse / Ephrin signaling / G alpha (i) signalling events / GP1b-IX-V activation signalling / Recycling pathway of L1 / Thrombin signalling through proteinase activated receptors (PARs) / VEGFR2 mediated cell proliferation / RAF activation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RET signaling / Receptor Mediated Mitophagy / ADP signalling through P2Y purinoceptor 1 / Downregulation of ERBB4 signaling / EPH-ephrin mediated repulsion of cells / Cyclin D associated events in G1 / Regulation of RUNX3 expression and activity / Activated NTRK3 signals through PI3K / Downstream signal transduction / MAP2K and MAPK activation / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / connexin binding / osteoclast development / progesterone receptor signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / bone resorption / extrinsic component of cytoplasmic side of plasma membrane / negative regulation of extrinsic apoptotic signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / epidermal growth factor receptor signaling pathway / cell junction / protein phosphatase binding / protein tyrosine kinase activity / mitochondrial inner membrane / cell differentiation / cytoskeleton / endosome membrane / regulation of cell cycle / cell adhesion / cell cycle / phosphorylation / signaling receptor binding / focal adhesion / innate immune response / heme binding / perinuclear region of cytoplasm / protein-containing complex / ATP binding / membrane / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Gallus gallus (chicken) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.39 Å | ||||||
Authors | Blair, J.A. / Apsel, B. / Knight, Z.A. / Shokat, K.M. | ||||||
Citation | Journal: Nat.Chem.Biol. / Year: 2008 Title: Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Authors: Apsel, B. / Blair, J.A. / Gonzalez, B. / Nazif, T.M. / Feldman, M.E. / Aizenstein, B. / Hoffman, R. / Williams, R.L. / Shokat, K.M. / Knight, Z.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3en6.cif.gz | 106.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3en6.ent.gz | 80 KB | Display | PDB format |
PDBx/mmJSON format | 3en6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/en/3en6 ftp://data.pdbj.org/pub/pdb/validation_reports/en/3en6 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 32726.645 Da / Num. of mol.: 2 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Details: Expression plasmid is pET28a modified to yield an N-terminal, tobacco etch virus (TEV) protease cleavable His6 tag Source: (gene. exp.) Gallus gallus (chicken) / Gene: SRC / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: P00523, non-specific protein-tyrosine kinase #2: Chemical | ChemComp-KS5 / | #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.99 Å3/Da / Density % sol: 58.85 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 14 mg/mL kinase, 50 mM Tris-HCl, 100 mM NaCl, 5% (v/v) glycerol mixed 1:1 with 20% (w/v) glycerol precipitant well solution, pH 8.0, vapor diffusion, hanging drop, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 8.2.1 / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 1, 2007 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: KOHZU: Double Crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.39→50 Å / Num. obs: 28471 / % possible obs: 96.1 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.082 / Net I/σ(I): 14.475 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.39→43.22 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.906 / Occupancy max: 1 / Occupancy min: 1 / SU B: 15.253 / SU ML: 0.162 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.291 / ESU R Free: 0.238 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 27.028 Å2
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Refinement step | Cycle: LAST / Resolution: 2.39→43.22 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.39→2.455 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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