+Open data
-Basic information
Entry | Database: PDB / ID: 5caq | ||||||
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Title | EGFR kinase domain mutant "TMLR" with compound 33 | ||||||
Components | Epidermal growth factor receptor | ||||||
Keywords | Transferase/transferase inhibitor / protein kinase inhibitor / Transferase-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 phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / 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 / regulation of peptidyl-tyrosine 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 / EGFR Transactivation by Gastrin / cellular response to cadmium ion / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / positive regulation of DNA repair / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / neurogenesis / cellular response to dexamethasone stimulus / ossification / positive regulation of synaptic transmission, glutamatergic / regulation of ERK1 and ERK2 cascade / neuron projection morphogenesis / basal plasma membrane / positive regulation of epithelial cell proliferation / 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 / astrocyte activation / liver regeneration / positive regulation of protein localization to plasma membrane / EGFR downregulation / positive regulation of smooth muscle cell proliferation / cellular response to amino acid stimulus / 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 / 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 / cell-cell adhesion / ruffle membrane / positive regulation of miRNA transcription Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Eigenbrot, C. / Yu, C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study. Authors: Heald, R. / Bowman, K.K. / Bryan, M.C. / Burdick, D. / Chan, B. / Chan, E. / Chen, Y. / Clausen, S. / Dominguez-Fernandez, B. / Eigenbrot, C. / Elliott, R. / Hanan, E.J. / Jackson, P. / ...Authors: Heald, R. / Bowman, K.K. / Bryan, M.C. / Burdick, D. / Chan, B. / Chan, E. / Chen, Y. / Clausen, S. / Dominguez-Fernandez, B. / Eigenbrot, C. / Elliott, R. / Hanan, E.J. / Jackson, P. / Knight, J. / La, H. / Lainchbury, M. / Malek, S. / Mann, S. / Merchant, M. / Mortara, K. / Purkey, H. / Schaefer, G. / Schmidt, S. / Seward, E. / Sideris, S. / Shao, L. / Wang, S. / Yeap, K. / Yen, I. / Yu, C. / Heffron, T.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5caq.cif.gz | 140.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5caq.ent.gz | 109.7 KB | Display | PDB format |
PDBx/mmJSON format | 5caq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ca/5caq ftp://data.pdbj.org/pub/pdb/validation_reports/ca/5caq | HTTPS FTP |
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-Related structure data
Related structure data | 5c8kC 5c8mC 5c8nC 5calC 5canC 5caoC 5capC 5casC 5cauC 5cavC C: citing same article (ref.) |
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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: 37549.398 Da / Num. of mol.: 1 / Mutation: T790M, 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-SO4 / |
#3: Chemical | ChemComp-4ZJ / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.46 Å3/Da / Density % sol: 64.46 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: PEG 10000, erthylene glycol |
-Data collection
Diffraction | Mean temperature: 110 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 25, 2013 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→46.2 Å / Num. obs: 18103 / % possible obs: 99.66 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 5.6 % / Biso Wilson estimate: 49.2 Å2 / Rsym value: 0.06 / Net I/σ(I): 21 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→46.2 Å / Cor.coef. Fo:Fc: 0.9445 / Cor.coef. Fo:Fc free: 0.921 / SU R Cruickshank DPI: 0.259 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.258 / SU Rfree Blow DPI: 0.207 / SU Rfree Cruickshank DPI: 0.21
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Displacement parameters | Biso mean: 58.96 Å2
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Refine analyze | Luzzati coordinate error obs: 0.336 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.5→46.2 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.65 Å / Total num. of bins used: 9
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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