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Yorodumi- PDB-6jz0: Crystal structure of EGFR kinase domain in complex with compound 78 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6jz0 | ||||||
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Title | Crystal structure of EGFR kinase domain in complex with compound 78 | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE/INHIBITOR / kinase / ATP binding site / covalent bonding with ligand / 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 / 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: 2.86 Å | ||||||
Authors | Peng, Y.H. / Wu, J.S. / Wu, S.Y. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer. Authors: Lin, S.Y. / Chang Hsu, Y. / Peng, Y.H. / Ke, Y.Y. / Lin, W.H. / Sun, H.Y. / Shiao, H.Y. / Kuo, F.M. / Chen, P.Y. / Lien, T.W. / Chen, C.H. / Chu, C.Y. / Wang, S.Y. / Yeh, K.C. / Chen, C.P. / ...Authors: Lin, S.Y. / Chang Hsu, Y. / Peng, Y.H. / Ke, Y.Y. / Lin, W.H. / Sun, H.Y. / Shiao, H.Y. / Kuo, F.M. / Chen, P.Y. / Lien, T.W. / Chen, C.H. / Chu, C.Y. / Wang, S.Y. / Yeh, K.C. / Chen, C.P. / Hsu, T.A. / Wu, S.Y. / Yeh, T.K. / Chen, C.T. / Hsieh, H.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6jz0.cif.gz | 79.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6jz0.ent.gz | 57 KB | Display | PDB format |
PDBx/mmJSON format | 6jz0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jz/6jz0 ftp://data.pdbj.org/pub/pdb/validation_reports/jz/6jz0 | 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: 37247.078 Da / Num. of mol.: 1 / Fragment: UNP residues 696-1021 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR / Cell line (production host): High Five / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P00533, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-CKO / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.4 Å3/Da / Density % sol: 63.8 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 1.0M Ammonium citrate tribase, 0.1M Bis-Tris propane, pH7.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: NSRRC / Beamline: BL13C1 / Wavelength: 1 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Dec 21, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.86→30 Å / Num. obs: 11675 / % possible obs: 97.9 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.074 / Χ2: 1.062 / Net I/σ(I): 10.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1M17 Resolution: 2.86→26.496 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 25.69
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 163.68 Å2 / Biso mean: 65.3579 Å2 / Biso min: 26.71 Å2 | |||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.86→26.496 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 4
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