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Yorodumi- PDB-6i82: Crystal structure of partially phosphorylated RET V804M tyrosine ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6i82 | ||||||||||||
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Title | Crystal structure of partially phosphorylated RET V804M tyrosine kinase domain complexed with PDD00018412 | ||||||||||||
Components | Proto-oncogene tyrosine-protein kinase receptor Ret | ||||||||||||
Keywords | ONCOPROTEIN / inhibitor / kinase / proto-oncogene | ||||||||||||
Function / homology | Function and homology information Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / glial cell-derived neurotrophic factor receptor signaling pathway / posterior midgut development / ureter maturation / embryonic epithelial tube formation / lymphocyte migration into lymphoid organs / membrane protein proteolysis / positive regulation of peptidyl-serine phosphorylation of STAT protein / positive regulation of neuron maturation ...Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / glial cell-derived neurotrophic factor receptor signaling pathway / posterior midgut development / ureter maturation / embryonic epithelial tube formation / lymphocyte migration into lymphoid organs / membrane protein proteolysis / positive regulation of peptidyl-serine phosphorylation of STAT protein / positive regulation of neuron maturation / neuron cell-cell adhesion / enteric nervous system development / innervation / plasma membrane protein complex / neuron maturation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / response to pain / regulation of axonogenesis / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of cell size / RET signaling / regulation of cell adhesion / cellular response to retinoic acid / NPAS4 regulates expression of target genes / transmembrane receptor protein tyrosine kinase activity / axon guidance / receptor protein-tyrosine kinase / positive regulation of neuron projection development / cell surface receptor protein tyrosine kinase signaling pathway / activation of cysteine-type endopeptidase activity involved in apoptotic process / MAPK cascade / retina development in camera-type eye / signaling receptor activity / RAF/MAP kinase cascade / protein tyrosine kinase activity / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / early endosome / endosome membrane / positive regulation of cell migration / response to xenobiotic stimulus / axon / protein phosphorylation / neuronal cell body / dendrite / calcium ion binding / positive regulation of gene expression / positive regulation of DNA-templated transcription / signal transduction / ATP binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.05 Å | ||||||||||||
Authors | Burschowsky, D. / Seewooruthun, C. / Bayliss, R. / Carr, M.D. / Echalier, A. / Jordan, A.M. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2020 Title: Discovery and Optimization of wt-RET/KDR-Selective Inhibitors of RETV804MKinase. Authors: Newton, R. / Waszkowycz, B. / Seewooruthun, C. / Burschowsky, D. / Richards, M. / Hitchin, S. / Begum, H. / Watson, A. / French, E. / Hamilton, N. / Jones, S. / Lin, L.Y. / Waddell, I. / ...Authors: Newton, R. / Waszkowycz, B. / Seewooruthun, C. / Burschowsky, D. / Richards, M. / Hitchin, S. / Begum, H. / Watson, A. / French, E. / Hamilton, N. / Jones, S. / Lin, L.Y. / Waddell, I. / Echalier, A. / Bayliss, R. / Jordan, A.M. / Ogilvie, D. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6i82.cif.gz | 138.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6i82.ent.gz | 105.6 KB | Display | PDB format |
PDBx/mmJSON format | 6i82.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i8/6i82 ftp://data.pdbj.org/pub/pdb/validation_reports/i8/6i82 | HTTPS FTP |
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-Related structure data
Related structure data | 6i83C 2ivsS 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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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 35820.277 Da / Num. of mol.: 2 / Mutation: V804M Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RET, CDHF12, CDHR16, PTC, RET51 / Cell line (production host): HEK293F / Production host: Homo sapiens (human) References: UniProt: P07949, receptor protein-tyrosine kinase |
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-Non-polymers , 5 types, 235 molecules
#2: Chemical | #3: Chemical | ChemComp-EDO / #4: Chemical | ChemComp-FMT / #5: Chemical | ChemComp-CL / | #6: 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: 2.23 Å3/Da / Density % sol: 44.9 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: 0.1 M sodium citrate pH 4.5-5.5, 2.0 M sodium formate drop size 500 nl + 500 nl RET at 3 mg/ml in 20 mM Tris pH 8.0, 100 mM NaCl, 1 mM DTT PH range: 4.5-5.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.97949 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Feb 14, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97949 Å / Relative weight: 1 |
Reflection | Resolution: 2.05→45.89 Å / Num. obs: 38208 / % possible obs: 96.4 % / Redundancy: 3.1 % / CC1/2: 1 / Rmerge(I) obs: 0.08 / Net I/σ(I): 7.5 |
Reflection shell | Resolution: 2.05→2.11 Å / Redundancy: 2.1 % / Rmerge(I) obs: 0.47 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 2324 / CC1/2: 0.73 / % possible all: 75 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2IVS Resolution: 2.05→45.89 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.935 / SU B: 5.999 / SU ML: 0.153 / Cross valid method: THROUGHOUT / ESU R: 0.201 / ESU R Free: 0.178 / 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: 33.246 Å2
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Refinement step | Cycle: 1 / Resolution: 2.05→45.89 Å
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