+Open data
-Basic information
Entry | Database: PDB / ID: 5feq | ||||||
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Title | EGFR KINASE DOMAIN IN COMPLEX WITH A COVALENT AMINOBENZIMIDAZOLE | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Inhibitor / Covalently bound / T790M / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
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: 3.4 Å | ||||||
Authors | DiDonato, M. / Spraggon, G. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of ...Title: Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers. Authors: Lelais, G. / Epple, R. / Marsilje, T.H. / Long, Y.O. / McNeill, M. / Chen, B. / Lu, W. / Anumolu, J. / Badiger, S. / Bursulaya, B. / DiDonato, M. / Fong, R. / Juarez, J. / Li, J. / Manuia, M. ...Authors: Lelais, G. / Epple, R. / Marsilje, T.H. / Long, Y.O. / McNeill, M. / Chen, B. / Lu, W. / Anumolu, J. / Badiger, S. / Bursulaya, B. / DiDonato, M. / Fong, R. / Juarez, J. / Li, J. / Manuia, M. / Mason, D.E. / Gordon, P. / Groessl, T. / Johnson, K. / Jia, Y. / Kasibhatla, S. / Li, C. / Isbell, J. / Spraggon, G. / Bender, S. / Michellys, P.Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5feq.cif.gz | 136 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5feq.ent.gz | 104.7 KB | Display | PDB format |
PDBx/mmJSON format | 5feq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5feq_validation.pdf.gz | 702.5 KB | Display | wwPDB validaton report |
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Full document | 5feq_full_validation.pdf.gz | 704.8 KB | Display | |
Data in XML | 5feq_validation.xml.gz | 12.7 KB | Display | |
Data in CIF | 5feq_validation.cif.gz | 16.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fe/5feq ftp://data.pdbj.org/pub/pdb/validation_reports/fe/5feq | HTTPS FTP |
-Related structure data
Related structure data | 5fedC 5feeC 2jitS 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
#1: Protein | Mass: 37391.277 Da / Num. of mol.: 1 / Mutation: T790M Source method: isolated from a genetically manipulated source Details: The inhibitor is covalently linked to Cys797. / Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Plasmid: pFastBacHTc / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): Sf9 References: UniProt: P00533, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-5XH / ~{ |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.46 Å3/Da / Density % sol: 64.4 % / Description: Hexagonal crystals after 1-2 weeks. |
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Crystal grow | Temperature: 294 K / Method: vapor diffusion, sitting drop / pH: 7.25 Details: 100mM HEPES pH 7.25, 0.20M Lithium Sulphate, 32% PEG-3350 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.97648 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Feb 19, 2012 |
Radiation | Monochromator: Single crystal, cylindrically bent, Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97648 Å / Relative weight: 1 |
Reflection | Resolution: 3.4→50 Å / Num. obs: 7241 / % possible obs: 100 % / Redundancy: 6.1 % / Biso Wilson estimate: 97.54 Å2 / Rmerge(I) obs: 0.216 / Net I/σ(I): 10.4 |
Reflection shell | Resolution: 3.4→3.52 Å / Redundancy: 6.2 % / Rmerge(I) obs: 0.956 / Mean I/σ(I) obs: 2.18 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2JIT Resolution: 3.4→21.12 Å / Cor.coef. Fo:Fc: 0.9374 / Cor.coef. Fo:Fc free: 0.896 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.419
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Displacement parameters | Biso mean: 68.48 Å2
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Refine analyze | Luzzati coordinate error obs: 0.571 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 3.4→21.12 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.4→3.8 Å / Total num. of bins used: 5
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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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