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Yorodumi- PDB-7tvd: Crystal structure of the kinase domain of EGFR exon-19 (del-747-7... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7tvd | ||||||
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Title | Crystal structure of the kinase domain of EGFR exon-19 (del-747-749) mutant | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE / EGFR / exon-19 / kinase / ONCOPROTEIN | ||||||
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 / ERBB2 Activates PTK6 Signaling / morphogenesis of an epithelial fold / intracellular vesicle / Signaling by EGFR / response to cobalamin / negative regulation of epidermal growth factor receptor signaling pathway / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Signaling by ERBB4 / 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 glial cell proliferation / positive regulation of phosphorylation / 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 / EGFR Transactivation by Gastrin / positive regulation of DNA repair / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / neurogenesis / SHC1 events in ERBB2 signaling / cellular response to dexamethasone stimulus / ossification / positive regulation of synaptic transmission, glutamatergic / regulation of ERK1 and ERK2 cascade / basal plasma membrane / neuron projection morphogenesis / positive regulation of superoxide anion generation / epithelial cell proliferation / positive regulation of DNA replication / Signal transduction by L1 / cellular response to estradiol stimulus / positive regulation of epithelial cell proliferation / NOTCH3 Activation and Transmission of Signal to the Nucleus / liver regeneration / astrocyte activation / cellular response to amino acid stimulus / positive regulation of protein localization to plasma membrane / EGFR downregulation / positive regulation of smooth muscle cell proliferation / lung development / Signaling by ERBB2 TMD/JMD mutants / clathrin-coated endocytic vesicle membrane / Constitutive Signaling by EGFRvIII / positive regulation of MAP kinase activity / 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 / cell-cell adhesion / Downregulation of ERBB2 signaling / ruffle membrane / cellular response to reactive oxygen species Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.96 Å | ||||||
Authors | Ashtekar, K.D. / Stayrook, S.E. / Lemmon, M.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2022 Title: Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Authors: van Alderwerelt van Rosenburgh, I.K. / Lu, D.M. / Grant, M.J. / Stayrook, S.E. / Phadke, M. / Walther, Z. / Goldberg, S.B. / Politi, K. / Lemmon, M.A. / Ashtekar, K.D. / Tsutsui, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7tvd.cif.gz | 157.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7tvd.ent.gz | 104.1 KB | Display | PDB format |
PDBx/mmJSON format | 7tvd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tv/7tvd ftp://data.pdbj.org/pub/pdb/validation_reports/tv/7tvd | HTTPS FTP |
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-Related structure data
Related structure data | 1m17S 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: 38237.191 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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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.64 Å3/Da / Density % sol: 66.16 % |
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Crystal grow | Temperature: 289.15 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 28% PEG 400, 0.1 M Na Hepes pH 7.5, 0.2 M Calcium Chloride |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.97918 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Mar 19, 2019 / Details: undulator | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.96→105.66 Å / Num. obs: 11749 / % possible obs: 100 % / Redundancy: 36.1 % / CC1/2: 0.999 / Rmerge(I) obs: 0.259 / Rpim(I) all: 0.044 / Rrim(I) all: 0.263 / Net I/σ(I): 15.4 / Num. measured all: 423785 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / % possible all: 100
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1M17 Resolution: 2.96→74.71 Å / SU ML: 0.4085 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 35.9126 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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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 mean: 104.92 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.96→74.71 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: -60.3983808351 Å / Origin y: 7.60852047851 Å / Origin z: 25.513823797 Å
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Refinement TLS group | Selection details: all |