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Yorodumi- PDB-3f3w: Drug resistant cSrc kinase domain in complex with inhibitor RL45 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3f3w | ||||||
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Title | Drug resistant cSrc kinase domain in complex with inhibitor RL45 (Type II) | ||||||
Components | Proto-oncogene tyrosine-protein kinase Src | ||||||
Keywords | TRANSFERASE / Allosteric / Type II / DFG-out / Drug resistance mutation / Alternative splicing / ATP-binding / Kinase / 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 / 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 / DCC mediated attractive signaling / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / connexin binding / progesterone receptor signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / epidermal growth factor receptor signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cell junction / protein phosphatase binding / protein tyrosine kinase activity / cell differentiation / endosome membrane / cytoskeleton / regulation of cell cycle / cell adhesion / mitochondrial inner membrane / innate immune response / focal adhesion / signaling receptor binding / 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: 2.6 Å | ||||||
Authors | Grutter, C. / Kluter, S. / Getlik, M. / Rauh, D. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc Authors: Getlik, M. / Grutter, C. / Simard, J.R. / Kluter, S. / Rabiller, M. / Rode, H.B. / Robubi, A. / Rauh, D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3f3w.cif.gz | 119.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3f3w.ent.gz | 92 KB | Display | PDB format |
PDBx/mmJSON format | 3f3w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3f3w_validation.pdf.gz | 958.7 KB | Display | wwPDB validaton report |
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Full document | 3f3w_full_validation.pdf.gz | 977.2 KB | Display | |
Data in XML | 3f3w_validation.xml.gz | 22.8 KB | Display | |
Data in CIF | 3f3w_validation.cif.gz | 30.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/f3/3f3w ftp://data.pdbj.org/pub/pdb/validation_reports/f3/3f3w | HTTPS FTP |
-Related structure data
Related structure data | 3f3vC 3g5dC 2oiqS 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 32772.801 Da / Num. of mol.: 2 / Fragment: Kinase domain, UNP residues 251-533 / Mutation: T338M, S345C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Gallus gallus (chicken) / Plasmid: pSKB3 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 (DE3) References: UniProt: P00523, non-specific protein-tyrosine kinase #2: Chemical | #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: 3.01 Å3/Da / Density % sol: 59.09 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 10% PEG 20000, 15% glycerol, 85mM MES, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 90 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00473 Å |
Detector | Type: MARRESEARCH / Detector: CCD / Date: Sep 2, 2008 / Details: Dynamically bendable mirror |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.00473 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→40 Å / Num. all: 23507 / Num. obs: 23074 / % possible obs: 98.2 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 39.548 Å2 / Rmerge(I) obs: 0.066 / Net I/σ(I): 16.1 |
Reflection shell | Resolution: 2.6→2.7 Å / Rmerge(I) obs: 0.27 / Mean I/σ(I) obs: 5.7 / Num. measured obs: 9399 / Num. unique all: 2506 / Num. unique obs: 2442 / % possible all: 97.4 |
-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 Starting model: PDB ENTRY 2OIQ Resolution: 2.6→40 Å / Cor.coef. Fo:Fc: 0.915 / Cor.coef. Fo:Fc free: 0.865 / WRfactor Rfree: 0.281 / WRfactor Rwork: 0.221 / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.79 / SU B: 21.299 / SU ML: 0.229 / SU R Cruickshank DPI: 0.548 / SU Rfree: 0.325 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.544 / ESU R Free: 0.322 / 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 max: 61.93 Å2 / Biso mean: 17.864 Å2 / Biso min: 2 Å2
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Refinement step | Cycle: LAST / Resolution: 2.6→40 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.6→2.667 Å / Total num. of bins used: 20
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