+Open data
-Basic information
Entry | Database: PDB / ID: 4lrm | ||||||
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Title | EGFR D770_N771insNPG in complex with PD168393 | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | transferase/transferase inhibitor / EGFR / Kinase / PD168393 / 34-jab / 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 / ERBB2 Activates PTK6 Signaling / morphogenesis of an epithelial fold / 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 / 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 / SHC1 events in ERBB2 signaling / neurogenesis / cellular response to dexamethasone stimulus / ossification / positive regulation of synaptic transmission, glutamatergic / 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 / 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 / receptor protein-tyrosine kinase / negative regulation of protein catabolic process / cell-cell adhesion / cell surface receptor protein tyrosine kinase signaling pathway / Downregulation of ERBB2 signaling / ruffle membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.526 Å | ||||||
Authors | Yun, C.H. / Eck, M.J. | ||||||
Citation | Journal: Sci Transl Med / Year: 2013 Title: Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer. Authors: Yasuda, H. / Park, E. / Yun, C.H. / Sng, N.J. / Lucena-Araujo, A.R. / Yeo, W.L. / Huberman, M.S. / Cohen, D.W. / Nakayama, S. / Ishioka, K. / Yamaguchi, N. / Hanna, M. / Oxnard, G.R. / ...Authors: Yasuda, H. / Park, E. / Yun, C.H. / Sng, N.J. / Lucena-Araujo, A.R. / Yeo, W.L. / Huberman, M.S. / Cohen, D.W. / Nakayama, S. / Ishioka, K. / Yamaguchi, N. / Hanna, M. / Oxnard, G.R. / Lathan, C.S. / Moran, T. / Sequist, L.V. / Chaft, J.E. / Riely, G.J. / Arcila, M.E. / Soo, R.A. / Meyerson, M. / Eck, M.J. / Kobayashi, S.S. / Costa, D.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4lrm.cif.gz | 589.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4lrm.ent.gz | 489.9 KB | Display | PDB format |
PDBx/mmJSON format | 4lrm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lr/4lrm ftp://data.pdbj.org/pub/pdb/validation_reports/lr/4lrm | HTTPS FTP |
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-Related structure data
Related structure data | 4lqmC 2jiuS 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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Unit cell |
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-Components
#1: Protein | Mass: 37900.715 Da / Num. of mol.: 5 Fragment: Epidermal Growth Factor Receptor (unp residues 694-1022) 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 #2: Chemical | ChemComp-YUN / #3: 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: 3.07 Å3/Da / Density % sol: 59.93 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 0.1M Tris, 2% PEG400, 5mM tris(2-carboxyethyl)-phosphine (TCEP), pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 16, 2008 |
Radiation | Monochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97918 Å / Relative weight: 1 |
Reflection | Resolution: 3.5→50 Å / Num. all: 28970 / Num. obs: 24856 / % possible obs: 85.8 % / Observed criterion σ(I): -1.1 / Redundancy: 2.3 % / Rmerge(I) obs: 0.151 / Net I/σ(I): 5.6 |
Reflection shell | Resolution: 3.5→3.77 Å / Redundancy: 2 % / Rmerge(I) obs: 0.389 / Mean I/σ(I) obs: 1.7 / % possible all: 76.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 2JIU Resolution: 3.526→49.181 Å / SU ML: 0.52 / σ(F): 1.36 / Phase error: 28.43 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.526→49.181 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: 31.7361 Å / Origin y: 268.974 Å / Origin z: 24.4121 Å
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Refinement TLS group | Selection details: all |