[English] 日本語
![](img/lk-miru.gif)
- PDB-6tfz: Crystal Structure of EGFR T790M/V948R in Complex with Covalent Py... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6tfz | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Crystal Structure of EGFR T790M/V948R in Complex with Covalent Pyrrolopyrimidine 19 | ||||||||||||
![]() | Epidermal growth factor receptor | ||||||||||||
![]() | TRANSFERASE / HER2 / EGFR / covalent Inhibitors | ||||||||||||
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 / 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 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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 / EGFR Transactivation by Gastrin / positive regulation of DNA repair / 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 / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / basal plasma membrane / 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 / positive regulation of epithelial cell proliferation / NOTCH3 Activation and Transmission of Signal to the Nucleus / 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 / cell-cell adhesion Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Niggenaber, J. / Mueller, M.P. / Rauh, D. | ||||||||||||
Funding support | ![]()
| ||||||||||||
![]() | ![]() Title: Targeting Her2-insYVMA with Covalent Inhibitors-A Focused Compound Screening and Structure-Based Design Approach. Authors: Lategahn, J. / Hardick, J. / Grabe, T. / Niggenaber, J. / Jeyakumar, K. / Keul, M. / Tumbrink, H.L. / Becker, C. / Hodson, L. / Kirschner, T. / Klovekorn, P. / Ketzer, J. / Baumann, M. / ...Authors: Lategahn, J. / Hardick, J. / Grabe, T. / Niggenaber, J. / Jeyakumar, K. / Keul, M. / Tumbrink, H.L. / Becker, C. / Hodson, L. / Kirschner, T. / Klovekorn, P. / Ketzer, J. / Baumann, M. / Terheyden, S. / Unger, A. / Weisner, J. / Muller, M.P. / van Otterlo, W.A.L. / Bauer, S. / Rauh, D. | ||||||||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 241.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 191 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 24.9 KB | Display | |
Data in CIF | ![]() | 34.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6tfuC ![]() 6tfvC ![]() 6tfwC ![]() 6tfyC ![]() 6tg0C ![]() 6tg1C ![]() 5j9zS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 | ![]()
| ||||||||
2 | ![]()
| ||||||||
Unit cell |
|
-
Components
#1: Protein | Mass: 37963.910 Da / Num. of mol.: 2 / Mutation: T790M, V948R Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P00533, receptor protein-tyrosine kinase #2: Chemical | #3: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-EDO / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 2.31 Å3/Da / Density % sol: 46.83 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 30 % PEG3350, 100 mM MgSO4, 4 % ethylen glycole 7.5 mg/mL EGFR T790M/V948R (in 100 mM NaCl, 25 mM Tris-HCl, 10 % glycerol, 1 mM TCEP, pH 8.0) 1 ul reservoir + 1 ul protein solution) |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 24, 2018 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.915 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→45.1 Å / Num. obs: 53054 / % possible obs: 99 % / Redundancy: 13.29 % / CC1/2: 1 / Rrim(I) all: 0.073 / Net I/σ(I): 20.25 |
Reflection shell | Resolution: 1.8→1.9 Å / Redundancy: 14.02 % / Mean I/σ(I) obs: 2.51 / Num. unique obs: 7769 / CC1/2: 0.85 / Rrim(I) all: 1.055 / % possible all: 98.3 |
-
Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 5j9z Resolution: 1.8→45.1 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 20.21
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 95.09 Å2 / Biso mean: 34.9242 Å2 / Biso min: 16.12 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.8→45.1 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS params. | Method: refined / Origin x: -6.5784 Å / Origin y: 5.3908 Å / Origin z: 10.1417 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement TLS group |
|