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Yorodumi- PDB-8hv8: Crystal structure of EGFR_TMX in complex with covalently bound fr... -
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-Basic information
Entry | Database: PDB / ID: 8hv8 | ||||||
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Title | Crystal structure of EGFR_TMX in complex with covalently bound fragment 10 | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE / Epidermal growth factor receptor kinase / covalent fragments / mutant EGFR / anti-cancer | ||||||
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 / 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 / Respiratory syncytial virus (RSV) attachment and entry / 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 / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / MAP kinase kinase kinase activity / embryonic placenta development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / 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 / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / cellular response to cadmium ion / 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 / positive regulation of synaptic transmission, glutamatergic / ossification / cellular response to dexamethasone stimulus / basal plasma membrane / neurogenesis / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / positive regulation of superoxide anion generation / positive regulation of DNA replication / epithelial cell proliferation / Signal transduction by L1 / 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 / 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 / lung development / clathrin-coated endocytic vesicle membrane / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / Downregulation of ERBB2 signaling / kinase binding / ruffle membrane / positive regulation of miRNA transcription / cellular response to reactive oxygen species Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Dokurno, P. | ||||||
Funding support | 1items
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Citation | Journal: Rsc Med Chem / Year: 2023 Title: A covalent fragment-based strategy targeting a novel cysteine to inhibit activity of mutant EGFR kinase. Authors: Kuki, N. / Walmsley, D.L. / Kanai, K. / Takechi, S. / Yoshida, M. / Murakami, R. / Takano, K. / Tominaga, Y. / Takahashi, M. / Ito, S. / Nakao, N. / Angove, H. / Baker, L.M. / Carter, E. / ...Authors: Kuki, N. / Walmsley, D.L. / Kanai, K. / Takechi, S. / Yoshida, M. / Murakami, R. / Takano, K. / Tominaga, Y. / Takahashi, M. / Ito, S. / Nakao, N. / Angove, H. / Baker, L.M. / Carter, E. / Dokurno, P. / Le Strat, L. / Macias, A.T. / Molyneaux, C.A. / Murray, J.B. / Surgenor, A.E. / Hamada, T. / Hubbard, R.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8hv8.cif.gz | 80.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8hv8.ent.gz | 57.1 KB | Display | PDB format |
PDBx/mmJSON format | 8hv8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8hv8_validation.pdf.gz | 660.8 KB | Display | wwPDB validaton report |
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Full document | 8hv8_full_validation.pdf.gz | 668.3 KB | Display | |
Data in XML | 8hv8_validation.xml.gz | 15 KB | Display | |
Data in CIF | 8hv8_validation.cif.gz | 20.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hv/8hv8 ftp://data.pdbj.org/pub/pdb/validation_reports/hv/8hv8 | HTTPS FTP |
-Related structure data
Related structure data | 8hv1C 8hv2C 8hv3C 8hv4C 8hv5C 8hv6C 8hv7C 8hv9C 8hvaC 5edqS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 37533.332 Da / Num. of mol.: 1 / Mutation: T790M, C797S, L858R, E865A, E866A, K867A 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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#2: Chemical | ChemComp-PE5 / |
#3: Chemical | ChemComp-N99 / ~{ |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.32 Å3/Da / Density % sol: 62.9 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 0.1M TRIS pH 8.5, 0.15M Sodium citrate, 25%PEG400 |
-Data collection
Diffraction | Mean temperature: 110 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: BRUKER TURBO X-RAY SOURCE / Wavelength: 1.54184 Å |
Detector | Type: BRUKER PHOTON 100 / Detector: CMOS / Date: Jan 3, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54184 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→21.23 Å / Num. obs: 18367 / % possible obs: 99.8 % / Redundancy: 15.04 % / Rmerge(I) obs: 0.1632 / Net I/σ(I): 12.97 |
Reflection shell | Resolution: 2.2→2.3 Å / Redundancy: 12.08 % / Rmerge(I) obs: 0.7468 / Mean I/σ(I) obs: 1.96 / Num. unique obs: 3124 / % possible all: 100 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5EDQ Resolution: 2.4→20 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.894 / SU B: 8.472 / SU ML: 0.189 / Cross valid method: THROUGHOUT / ESU R: 0.311 / ESU R Free: 0.256 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 40.424 Å2
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Refinement step | Cycle: 1 / Resolution: 2.4→20 Å
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Refine LS restraints |
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