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- PDB-4rwl: Crystal structure of FGFR1 (C488A, C584C) in complex with 6-(7-((... -
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Basic information
Entry | Database: PDB / ID: 4rwl | ||||||
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Title | Crystal structure of FGFR1 (C488A, C584C) in complex with 6-(7-((1-aminocyclopropyl) methoxy)-6-methoxyquinolin-4-yloxy)-N-methyl-1-naphthamide (E3810) | ||||||
![]() | Fibroblast growth factor receptor 1 | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / receptor tyrosine kinase / gatekeeper mutation / proto-oncogene / kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() Signaling by FGFR1 amplification mutants / negative regulation of fibroblast growth factor production / positive regulation of mitotic cell cycle DNA replication / regulation of extrinsic apoptotic signaling pathway in absence of ligand / Signaling by plasma membrane FGFR1 fusions / diphosphate metabolic process / vitamin D3 metabolic process / FGFR1c and Klotho ligand binding and activation / regulation of phosphate transport / regulation of lateral mesodermal cell fate specification ...Signaling by FGFR1 amplification mutants / negative regulation of fibroblast growth factor production / positive regulation of mitotic cell cycle DNA replication / regulation of extrinsic apoptotic signaling pathway in absence of ligand / Signaling by plasma membrane FGFR1 fusions / diphosphate metabolic process / vitamin D3 metabolic process / FGFR1c and Klotho ligand binding and activation / regulation of phosphate transport / regulation of lateral mesodermal cell fate specification / positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway / cementum mineralization / response to sodium phosphate / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / receptor-receptor interaction / fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development / auditory receptor cell development / ventricular zone neuroblast division / Epithelial-Mesenchymal Transition (EMT) during gastrulation / positive regulation of parathyroid hormone secretion / chordate embryonic development / mesenchymal cell proliferation / paraxial mesoderm development / FGFR1b ligand binding and activation / fibroblast growth factor receptor activity / branching involved in salivary gland morphogenesis / Signaling by activated point mutants of FGFR1 / FGFR1c ligand binding and activation / organ induction / Downstream signaling of activated FGFR1 / Phospholipase C-mediated cascade: FGFR1 / positive regulation of phospholipase activity / lung-associated mesenchyme development / cell projection assembly / cellular response to fibroblast growth factor stimulus / outer ear morphogenesis / middle ear morphogenesis / embryonic limb morphogenesis / skeletal system morphogenesis / positive regulation of vascular endothelial cell proliferation / cardiac muscle cell proliferation / positive regulation of mesenchymal cell proliferation / positive regulation of endothelial cell chemotaxis / ureteric bud development / inner ear morphogenesis / midbrain development / regulation of cell differentiation / positive regulation of stem cell proliferation / fibroblast growth factor binding / Formation of paraxial mesoderm / PI-3K cascade:FGFR1 / phosphatidylinositol-mediated signaling / PI3K Cascade / positive regulation of blood vessel endothelial cell migration / epithelial to mesenchymal transition / fibroblast growth factor receptor signaling pathway / chondrocyte differentiation / : / calcium ion homeostasis / SHC-mediated cascade:FGFR1 / positive regulation of cardiac muscle cell proliferation / cell maturation / FRS-mediated FGFR1 signaling / Signaling by FGFR1 in disease / positive regulation of neuron differentiation / NCAM signaling for neurite out-growth / SH2 domain binding / stem cell proliferation / Signal transduction by L1 / skeletal system development / stem cell differentiation / positive regulation of cell differentiation / sensory perception of sound / Negative regulation of FGFR1 signaling / positive regulation of MAP kinase activity / neuron migration / receptor protein-tyrosine kinase / positive regulation of neuron projection development / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / MAPK cascade / neuron projection development / cell migration / PIP3 activates AKT signaling / heparin binding / gene expression / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cytoplasmic vesicle / RAF/MAP kinase cascade / protein tyrosine kinase activity / angiogenesis / in utero embryonic development / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / protein phosphorylation / positive regulation of cell population proliferation / negative regulation of transcription by RNA polymerase II / protein homodimerization activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Sohl, C.D. / Anderson, K.S. | ||||||
![]() | ![]() Title: Illuminating the Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance for the FGFR1 Gatekeeper Mutation: The Achilles' Heel of Targeted Therapy. Authors: Sohl, C.D. / Ryan, M.R. / Luo, B. / Frey, K.M. / Anderson, K.S. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 124.3 KB | Display | ![]() |
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PDB format | ![]() | 94.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 4rwiC ![]() 4rwjC ![]() 4rwkC ![]() 4nkaS C: citing same article ( S: Starting model for refinement |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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Components
#1: Protein | Mass: 36226.602 Da / Num. of mol.: 2 / Fragment: Residues 458-765 / Mutation: C488A, C584S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P11362, receptor protein-tyrosine kinase #2: Chemical | ChemComp-3ZC / | #3: Chemical | ChemComp-SO4 / | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.59 Å3/Da / Density % sol: 52.59 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.6 Details: 0.1 M sodium cacodylate pH 6.6, 34% PEG 8000, 0.2 M ammonium sulfate, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 77 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 22, 2014 / Details: monochrometer | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Cryogenically cooled double crystal monochrometer with horizontal focusing sagittal bend second mono crystal with 4:1 magnification ratio and vertically focusing mirror. Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.075 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.19→50 Å / Num. obs: 38180 / % possible obs: 99.1 % / Observed criterion σ(I): -3 / Redundancy: 3.7 % / Biso Wilson estimate: 40.93 Å2 / Rsym value: 0.086 / Net I/σ(I): 31.88 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4NKA Resolution: 2.193→32.986 Å / SU ML: 0.27 / σ(F): 1.34 / Phase error: 28.32 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 47.8932 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.193→32.986 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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LS refinement shell |
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