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Yorodumi- PDB-4i21: Crystal structure of L858R + T790M EGFR kinase domain in complex ... -
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-Basic information
Entry | Database: PDB / ID: 4i21 | ||||||
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Title | Crystal structure of L858R + T790M EGFR kinase domain in complex with MIG6 peptide | ||||||
Components |
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Keywords | Transferase/Transferase Inhibitor / EGFR kinase domain / Phosphotransfer / MIG6 peptide / ATP binding / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information response to 1-oleoyl-sn-glycerol 3-phosphate / uterine epithelium development / limb joint morphogenesis / negative regulation of epidermal growth factor-activated receptor activity / lung vasculature development / lung epithelium development / regulation of keratinocyte differentiation / chondrocyte proliferation / negative regulation of protein autophosphorylation / bile acid biosynthetic process ...response to 1-oleoyl-sn-glycerol 3-phosphate / uterine epithelium development / limb joint morphogenesis / negative regulation of epidermal growth factor-activated receptor activity / lung vasculature development / lung epithelium development / regulation of keratinocyte differentiation / chondrocyte proliferation / negative regulation of protein autophosphorylation / bile acid biosynthetic process / skin morphogenesis / tissue homeostasis / cartilage development / 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 / fat pad development / 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 / lung alveolus development / 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 / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein insertion into membrane / eyelid development in camera-type eye / cerebral cortex cell migration / progesterone receptor signaling pathway / ERBB2 Regulates Cell Motility / regulation of JNK cascade / activation of phospholipase C activity / positive regulation of cyclin-dependent protein serine/threonine kinase activity / PI3K events in ERBB2 signaling / negative regulation of mitotic cell cycle / hair follicle development / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of G1/S transition of mitotic cell cycle / embryonic placenta development / positive regulation of bone resorption / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / salivary gland morphogenesis / regulation of peptidyl-tyrosine phosphorylation / peptidyl-tyrosine autophosphorylation / positive regulation of glial cell proliferation / positive regulation of phosphorylation / positive regulation of vasoconstriction / embryo implantation / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / cellular response to cadmium ion / cholesterol metabolic process / positive regulation of DNA repair / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in ERBB2 signaling / transmembrane receptor protein tyrosine kinase activity / GTPase activator activity / neurogenesis / cellular response to dexamethasone stimulus / SHC1 events in ERBB2 signaling / ossification / positive regulation of synaptic transmission, glutamatergic / basal plasma membrane / regulation of ERK1 and ERK2 cascade / cholesterol homeostasis / neuron projection morphogenesis / positive regulation of superoxide anion generation / response to progesterone / liver development / positive regulation of DNA replication / phosphatidylinositol 3-kinase/protein kinase B signal transduction / Signal transduction by L1 / epithelial cell proliferation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.37 Å | ||||||
Authors | Gajiwala, K.S. / Feng, J. / Ferre, R. / Ryan, K. / Brodsky, O. / Stewart, A. | ||||||
Citation | Journal: Structure / Year: 2013 Title: Insights into the Aberrant Activity of Mutant EGFR Kinase Domain and Drug Recognition. Authors: Gajiwala, K.S. / Feng, J. / Ferre, R. / Ryan, K. / Brodsky, O. / Weinrich, S. / Kath, J.C. / Stewart, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4i21.cif.gz | 140.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4i21.ent.gz | 109.9 KB | Display | PDB format |
PDBx/mmJSON format | 4i21.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i2/4i21 ftp://data.pdbj.org/pub/pdb/validation_reports/i2/4i21 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 37522.387 Da / Num. of mol.: 2 / Fragment: UNP residues 695-1022, EGFR kinase domain / Mutation: L858R, 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: Protein | Mass: 6599.357 Da / Num. of mol.: 2 / Fragment: UNP residues 315-374 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ERRFI1, MIG6 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UJM3 |
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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: 2.5 Å3/Da / Density % sol: 50.79 % |
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Crystal grow | Temperature: 294 K / Method: vapor diffusion, hanging drop Details: 14.5% PEG 8,000, 0.1M Na Acetate trihydrate pH 4.8-5.5, 0.2-0.38 M K acetate, VAPOR DIFFUSION, HANGING DROP, temperature 294K PH range: 4.8 - 5.5 |
-Data collection
Diffraction | Mean temperature: 98 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Jun 9, 2011 / Details: Mirrors |
Radiation | Monochromator: Mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 3.37→42.99 Å / Num. all: 12057 / Num. obs: 11744 / % possible obs: 97.4 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.5 % / Rmerge(I) obs: 0.085 / Net I/σ(I): 10 |
Reflection shell | Resolution: 3.37→3.56 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.399 / Mean I/σ(I) obs: 2.6 / Num. unique all: 1723 / % possible all: 96.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 3.37→37.18 Å / Rfactor Rfree error: 0.011 / Data cutoff high absF: 590966.42 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 59.8752 Å2 / ksol: 0.325091 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 69.9 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 3.37→37.18 Å
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Refine LS restraints |
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Refine LS restraints NCS | Weight Biso : 2 / Weight position: 300 | ||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 3.37→3.58 Å / Rfactor Rfree error: 0.037 / Total num. of bins used: 6
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Xplor file |
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