[English] 日本語
Yorodumi- PDB-2rgp: Structure of EGFR in complex with hydrazone, a potent dual inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 2rgp | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of EGFR in complex with hydrazone, a potent dual inhibitor | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | TRANSFERASE / Kinase domain / Alternative splicing / Anti-oncogene / ATP-binding / Cell cycle / Disease mutation / Glycoprotein / Membrane / Nucleotide-binding / Phosphoprotein / Polymorphism / Receptor / Secreted / Transmembrane / Tyrosine-protein kinase / Ubl conjugation | ||||||
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 / tongue development / Inhibition of Signaling by Overexpressed EGFR ...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 / tongue development / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / epidermal growth factor binding / response to UV-A / PLCG1 events in ERBB2 signaling / midgut development / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / response to cobalamin / Signaling by ERBB4 / 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 / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / embryonic placenta development / positive regulation of bone resorption / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / cellular response to cadmium ion / EGFR Transactivation by Gastrin / transmembrane receptor protein tyrosine kinase activity / GRB2 events in ERBB2 signaling / positive regulation of DNA repair / SHC1 events in ERBB2 signaling / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / positive regulation of synaptic transmission, glutamatergic / neuron projection morphogenesis / basal plasma membrane / positive regulation of epithelial cell proliferation / epithelial cell proliferation / positive regulation of superoxide anion generation / positive regulation of DNA replication / Signal transduction by L1 / cellular response to estradiol stimulus / liver regeneration / NOTCH3 Activation and Transmission of Signal to the Nucleus / astrocyte activation / positive regulation of protein localization to plasma membrane / Signaling by ERBB2 TMD/JMD mutants / cellular response to amino acid stimulus / positive regulation of smooth muscle cell proliferation / EGFR downregulation / lung development / clathrin-coated endocytic vesicle membrane / positive regulation of MAP kinase activity / Constitutive Signaling by EGFRvIII / negative regulation of protein catabolic process / Signaling by ERBB2 ECD mutants / epidermal growth factor receptor signaling pathway / Signaling by ERBB2 KD Mutants / receptor protein-tyrosine kinase / kinase binding / Downregulation of ERBB2 signaling / cell-cell adhesion / positive regulation of miRNA transcription / ruffle membrane / HCMV Early Events Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2 Å | ||||||
Authors | Abad, M.C. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2008 Title: 4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors. Authors: Xu, G. / Abad, M.C. / Connolly, P.J. / Neeper, M.P. / Struble, G.T. / Springer, B.A. / Emanuel, S.L. / Pandey, N. / Gruninger, R.H. / Adams, M. / Moreno-Mazza, S. / Fuentes-Pesquera, A.R. / Middleton, S.A. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 2rgp.cif.gz | 75.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb2rgp.ent.gz | 54.5 KB | Display | PDB format |
PDBx/mmJSON format | 2rgp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 2rgp_validation.pdf.gz | 741.6 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 2rgp_full_validation.pdf.gz | 752.1 KB | Display | |
Data in XML | 2rgp_validation.xml.gz | 14.4 KB | Display | |
Data in CIF | 2rgp_validation.cif.gz | 19.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rg/2rgp ftp://data.pdbj.org/pub/pdb/validation_reports/rg/2rgp | HTTPS FTP |
-Related structure data
Related structure data | 1xkkS S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 36070.809 Da / Num. of mol.: 1 / Fragment: Residues 702-1016 Source method: isolated from a genetically manipulated source Details: Expressed open reading frame of construct is MHHHHHHVDLVPRGSHMA-(EGFR1 S671-G998 Source: (gene. exp.) Homo sapiens (human) / Strain: human strains undefined / Gene: EGFR, ERBB1 / Plasmid: modified pDEST8 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): sf9 References: UniProt: P00533, receptor protein-tyrosine kinase | ||||
---|---|---|---|---|---|
#2: Chemical | #3: Chemical | ChemComp-HYZ / | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.25 Å3/Da / Density % sol: 45.22 % |
---|---|
Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 9 Details: 2M Na/K3PO4, 0.1M Caps pH 9.0 and 0.2M Li2SO4, VAPOR DIFFUSION, HANGING DROP, temperature 295K |
-Data collection
Diffraction | Mean temperature: 200 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Feb 22, 2005 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.89→50 Å / Num. obs: 26482 / % possible obs: 98.9 % / Redundancy: 3.9 % / Biso Wilson estimate: 33 Å2 / Rmerge(I) obs: 0.046 / Χ2: 1.571 / Net I/σ(I): 15.8 |
Reflection shell | Resolution: 2.04→2.13 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.208 / Mean I/σ(I) obs: 7.28 / Num. unique all: 2508 / Χ2: 1.161 / % possible all: 99.9 |
-Phasing
Phasing | Method: molecular replacement |
---|
-Processing
Software |
| ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1XKK Resolution: 2→50 Å / FOM work R set: 0.793 / Isotropic thermal model: anisotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0
| ||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 44.528 Å2
| ||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2→50 Å
| ||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||
Xplor file |
|