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Yorodumi- PDB-5yu9: Crystal structure of EGFR 696-1022 T790M in complex with Ibrutinib -
+Open data
-Basic information
Entry | Database: PDB / ID: 5yu9 | ||||||
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Title | Crystal structure of EGFR 696-1022 T790M in complex with Ibrutinib | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | ONCOPROTEIN / EGFR / T790M / ibrutinib / inhibitor | ||||||
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: 1.95 Å | ||||||
Authors | Yan, X.E. / Yun, C.H. | ||||||
Citation | Journal: Oncotarget / Year: 2016 Title: Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation. Authors: Wang, A. / Yan, X.E. / Wu, H. / Wang, W. / Hu, C. / Chen, C. / Zhao, Z. / Zhao, P. / Li, X. / Wang, L. / Wang, B. / Ye, Z. / Wang, J. / Wang, C. / Zhang, W. / Gray, N.S. / Weisberg, E.L. / ...Authors: Wang, A. / Yan, X.E. / Wu, H. / Wang, W. / Hu, C. / Chen, C. / Zhao, Z. / Zhao, P. / Li, X. / Wang, L. / Wang, B. / Ye, Z. / Wang, J. / Wang, C. / Zhang, W. / Gray, N.S. / Weisberg, E.L. / Chen, L. / Liu, J. / Yun, C.H. / Liu, Q. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5yu9.cif.gz | 277.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5yu9.ent.gz | 221.4 KB | Display | PDB format |
PDBx/mmJSON format | 5yu9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yu/5yu9 ftp://data.pdbj.org/pub/pdb/validation_reports/yu/5yu9 | HTTPS FTP |
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-Related structure data
Related structure data | 3ikaS 4ynj 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 37650.598 Da / Num. of mol.: 4 / Mutation: T790M 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-1E8 / #3: Chemical | #4: 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: 2.2 Å3/Da / Density % sol: 44.04 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5 Details: 0.1 M sodium citrate (pH 5.0), 12% PEG 10000, 3% dioxane, 5 mM TCEP |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.9793 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jan 26, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→50 Å / Num. obs: 94954 / % possible obs: 99.42 % / Redundancy: 3.2 % / Rpim(I) all: 0.095 / Net I/σ(I): 7.9 |
Reflection shell | Resolution: 1.95→2.02 Å |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3IKA Resolution: 1.95→41.628 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.98 / Phase error: 22.95 / 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: 1.95→41.628 Å
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Refine LS restraints |
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LS refinement shell |
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