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- PDB-8po2: Discovery and Optimisation of Potent, Efficacious and Selective I... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8po2 | ||||||
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Title | Discovery and Optimisation of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations. Compound 33 bound to EGFRinsNPG [V948R] | ||||||
![]() | Epidermal growth factor receptor | ||||||
![]() | SIGNALING PROTEIN / EGFR / Exon 20 insertion / non-small cell lung cancer / oncology | ||||||
Function / homology | ![]() 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 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / 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 / 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 / cellular response to dexamethasone stimulus / ossification / neurogenesis / 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 / lung development / positive regulation of MAP kinase activity / 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Hargreaves, D. | ||||||
Funding support | 1items
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![]() | ![]() Title: Discovery and Optimization of Potent, Efficacious and Selective Inhibitors Targeting EGFR Exon20 Insertion Mutations. Authors: Thomson, C. / Barton, P. / Braybrooke, E. / Colclough, N. / Dong, Z. / Evans, L. / Floc'h, N. / Guerot, C. / Hargreaves, D. / Khurana, P. / Li, S. / Li, X. / Lister, A. / McCoull, W. / ...Authors: Thomson, C. / Barton, P. / Braybrooke, E. / Colclough, N. / Dong, Z. / Evans, L. / Floc'h, N. / Guerot, C. / Hargreaves, D. / Khurana, P. / Li, S. / Li, X. / Lister, A. / McCoull, W. / McWilliams, L. / Orme, J.P. / Packer, M.J. / Swaih, A.M. / Ward, R.A. / Winlow, P. / Ye, Y. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 138.9 KB | Display | ![]() |
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PDB format | ![]() | 103.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 8pnzC ![]() 8po0C ![]() 8po1C ![]() 8po3C ![]() 8po4C C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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2 | ![]()
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3 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 37774.594 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Details: flexible C-terminal belonging to either chain A or chain B Source: (gene. exp.) ![]() Production host: ![]() References: UniProt: P00533, receptor protein-tyrosine kinase #2: Chemical | Mass: 481.549 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H27N7O2 / Feature type: SUBJECT OF INVESTIGATION #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.16 Å3/Da / Density % sol: 42.97 % / Description: stacks of plate-like crystals |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / Details: PEG 8K 15%w/v pH 0, PCPT 0.1M pH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 28, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97625 Å / Relative weight: 1 |
Reflection | Resolution: 2.28→69.06 Å / Num. obs: 104467 / % possible obs: 92.7 % / Redundancy: 3.3 % / CC1/2: 0.996 / Net I/σ(I): 9.6 |
Reflection shell | Resolution: 2.28→2.47 Å / Num. unique obs: 1565 / CC1/2: 0.476 |
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Processing
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Refinement | Method to determine structure: ![]()
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Displacement parameters | Biso mean: 44.88 Å2
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Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.28→69.06 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.28→2.38 Å
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