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Yorodumi- PDB-8a27: EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8a27 | ||||||
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Title | EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-1-oxo-4-(trifluoromethyl)isoindolin-2-yl]-N-thiazol-2-yl-acetamide | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE / KINASE INHIBITOR | ||||||
Function / homology | Function and homology information Complex I biogenesis / Respiratory electron transport / : / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / NADH dehydrogenase (ubiquinone) activity / aerobic respiration / electron transfer activity / mitochondrial inner membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.07 Å | ||||||
Authors | Kuglstatter, A. / Ehler, A. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Discovery of Novel Allosteric EGFR L858R Inhibitors for the Treatment of Non-Small-Cell Lung Cancer as a Single Agent or in Combination with Osimertinib. Authors: Obst-Sander, U. / Ricci, A. / Kuhn, B. / Friess, T. / Koldewey, P. / Kuglstatter, A. / Hewings, D. / Goergler, A. / Steiner, S. / Rueher, D. / Imhoff, M.P. / Raschetti, N. / Marty, H.P. / ...Authors: Obst-Sander, U. / Ricci, A. / Kuhn, B. / Friess, T. / Koldewey, P. / Kuglstatter, A. / Hewings, D. / Goergler, A. / Steiner, S. / Rueher, D. / Imhoff, M.P. / Raschetti, N. / Marty, H.P. / Dietzig, A. / Rynn, C. / Ehler, A. / Burger, D. / Kornacker, M. / Schaffland, J.P. / Herting, F. / Pao, W. / Bischoff, J.R. / Martoglio, B. / Alice Nagel, Y. / Jaeschke, G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8a27.cif.gz | 151.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8a27.ent.gz | 115.9 KB | Display | PDB format |
PDBx/mmJSON format | 8a27.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a2/8a27 ftp://data.pdbj.org/pub/pdb/validation_reports/a2/8a27 | HTTPS FTP |
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-Related structure data
Related structure data | 8a2aC 8a2bC 8a2dC 5hg8S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 37225.098 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P00533, receptor protein-tyrosine kinase | ||||||||
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#2: Chemical | #3: Chemical | ChemComp-KY9 / ( | #4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.84 Å3/Da / Density % sol: 32.98 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 20% PEG Smear Medium, 0.1M MES, 0.15 ammonium nitrate, 5% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.9999 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 2, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9999 Å / Relative weight: 1 |
Reflection | Resolution: 1.07→65.61 Å / Num. obs: 86262 / % possible obs: 92.5 % / Redundancy: 5 % / CC1/2: 1 / Net I/σ(I): 13.1 |
Reflection shell | Resolution: 1.07→1.16 Å / Num. unique obs: 4541 / CC1/2: 0.66 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5hg8 Resolution: 1.07→65.61 Å / Cor.coef. Fo:Fc: 0.984 / Cor.coef. Fo:Fc free: 0.976 / SU B: 1.212 / SU ML: 0.024 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.031 / ESU R Free: 0.034 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: 122.47 Å2 / Biso mean: 16.31 Å2 / Biso min: 6.33 Å2
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Refinement step | Cycle: final / Resolution: 1.07→65.61 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.072→1.1 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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