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Yorodumi- PDB-7k1i: EGFR kinase (L858R/V948R) in complex with allosteric inhibitor JB... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7k1i | |||||||||
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Title | EGFR kinase (L858R/V948R) in complex with allosteric inhibitor JBJ-09-063 | |||||||||
Components | Epidermal growth factor receptor | |||||||||
Keywords | TRANSFERASE/TRANSFERASE Inhibitor / EGFR / ErbB1 / kinase / inhibitor / TRANSFERASE / TRANSFERASE-TRANSFERASE Inhibitor complex | |||||||||
Function / homology | Function and homology information response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity ...response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / regulation of nitric-oxide synthase activity / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / eyelid development in camera-type eye / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / cellular response to cadmium ion / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / positive regulation of DNA repair / EGFR Transactivation by Gastrin / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / ossification / positive regulation of synaptic transmission, glutamatergic / neurogenesis / cellular response to dexamethasone stimulus / basal plasma membrane / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of DNA replication / Signal transduction by L1 / epithelial cell proliferation / cellular response to estradiol stimulus / NOTCH3 Activation and Transmission of Signal to the Nucleus / positive regulation of epithelial cell proliferation / astrocyte activation / liver regeneration / positive regulation of protein localization to plasma membrane / EGFR downregulation / cell surface receptor protein tyrosine kinase signaling pathway / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / Signaling by ERBB2 TMD/JMD mutants / positive regulation of MAP kinase activity / clathrin-coated endocytic vesicle membrane / lung development / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / Downregulation of ERBB2 signaling / kinase binding / ruffle membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.202 Å | |||||||||
Authors | Beyett, T.S. / Eck, M.J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2022 Title: Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors Authors: Beyett, T.S. / To, C. / Heppner, D.E. / Rana, J.K. / Schmoker, A.M. / Jang, J. / De Clercq, D.J.H. / Gomez, G. / Scott, D.A. / Gray, N.S. / Janne, P.A. / Eck, M.J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7k1i.cif.gz | 144.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7k1i.ent.gz | 110.1 KB | Display | PDB format |
PDBx/mmJSON format | 7k1i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k1/7k1i ftp://data.pdbj.org/pub/pdb/validation_reports/k1/7k1i | HTTPS FTP |
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-Related structure data
Related structure data | 7jxiC 7jxkC 7jxlC 7jxmC 7jxpC 7jxwC 7k1hC 5d41S S: Starting model for refinement C: citing same article (ref.) |
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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: 37738.539 Da / Num. of mol.: 1 / Fragment: kinase domain / Mutation: L858R, V948R Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Plasmid: pTriEX / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P00533, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-MG / |
#3: Chemical | ChemComp-ANP / |
#4: Chemical | ChemComp-VNS / ( |
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: 1.89 Å3/Da / Density % sol: 35.04 % / Mosaicity: 0 ° |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5 / Details: 0.1 M Bis-Tris pH 5.5, 28% (w/v) PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9792 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 5, 2018 | |||||||||||||||||||||||||||
Radiation | Monochromator: Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 3.2→53.94 Å / Num. obs: 4805 / % possible obs: 98.8 % / Redundancy: 6.5 % / Biso Wilson estimate: 114.45 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.144 / Rpim(I) all: 0.062 / Rrim(I) all: 0.158 / Net I/σ(I): 7.2 / Num. measured all: 31390 / Scaling rejects: 27 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Redundancy: 5.8 %
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5D41 Resolution: 3.202→53.936 Å / SU ML: 0.39 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 29.51 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 365.42 Å2 / Biso mean: 153.8804 Å2 / Biso min: 30 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 3.202→53.936 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Origin x: 17.3615 Å / Origin y: -14.9412 Å / Origin z: 8.3435 Å
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Refinement TLS group | Selection details: (chain 'A' and resid 700 through 1007) |