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- PDB-6b3s: Crystal structure of the Fab fragment of necitumumab (Fab11F8) in... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6b3s | |||||||||
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Title | Crystal structure of the Fab fragment of necitumumab (Fab11F8) in complex with domain III from a cetuximab resistant variant of EGFR (sEGFRd3-S468R) | |||||||||
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![]() | TRANSFERASE/immune system / Therapeutic antibody / Cetuximab resistance / Somatic mutation / Colorectal cancer / TRANSFERASE / TRANSFERASE-immune system complex | |||||||||
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 / 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 | ![]() | |||||||||
Method | ![]() ![]() ![]() | |||||||||
![]() | Ferguson, K.M. / Bagchi, A. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance. Authors: Bagchi, A. / Haidar, J.N. / Eastman, S.W. / Vieth, M. / Topper, M. / Iacolina, M.D. / Walker, J.M. / Forest, A. / Shen, Y. / Novosiadly, R.D. / Ferguson, K.M. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 476.4 KB | Display | ![]() |
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PDB format | ![]() | 389.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 3b2uS S: Starting model for refinement |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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2 | ![]()
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3 | ![]()
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4 | ![]()
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Unit cell |
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Components
-Antibody , 2 types, 8 molecules HCFJLDGK
#2: Antibody | Mass: 23547.330 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Antibody | Mass: 23053.557 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Protein / Non-polymers , 2 types, 73 molecules ABEI![](data/chem/img/HOH.gif)
![](data/chem/img/HOH.gif)
#1: Protein | Mass: 23856.203 Da / Num. of mol.: 4 / Mutation: S468R Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P00533, receptor protein-tyrosine kinase #8: Water | ChemComp-HOH / | |
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-Sugars , 4 types, 15 molecules ![](data/chem/img/NAG.gif)
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.76 Å3/Da / Density % sol: 67.31 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 50 mM sodium acetate, 200 mM potassium citrate, 15-20% PEG3350 PH range: 6.0-6.3 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 15, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 2.795→50 Å / Num. obs: 100220 / % possible obs: 97 % / Redundancy: 4.2 % / Biso Wilson estimate: 63.32 Å2 / Rmerge(I) obs: 0.162 / Net I/σ(I): 6 |
Reflection shell | Resolution: 2.8→2.93 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.703 / % possible all: 94.9 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3B2U Resolution: 2.8→47 Å / SU ML: 0.39 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 28.91
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 73.81 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.8→47 Å
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Refine LS restraints |
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LS refinement shell |
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