+Open data
-Basic information
Entry | Database: PDB / ID: 5am7 | |||||||||
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Title | FGFR1 mutant with an inhibitor | |||||||||
Components | FIBROBLAST GROWTH FACTOR RECEPTOR 1 | |||||||||
Keywords | TRANSFERASE / FGFR / CANCER / DOVITINIB / TKI258 / GATEKEEPER / GATE KEEPER | |||||||||
Function / homology | Function and homology information 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 / FGFR1c and Klotho ligand binding and activation / vitamin D3 metabolic process / 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 / FGFR1c and Klotho ligand binding and activation / vitamin D3 metabolic process / 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 / positive regulation of endothelial cell chemotaxis to fibroblast growth factor / receptor-receptor interaction / response to sodium phosphate / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / 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 / fibroblast growth factor receptor activity / FGFR1b ligand binding and activation / 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 / phosphatidylinositol-mediated signaling / outer ear morphogenesis / middle ear morphogenesis / embryonic limb morphogenesis / skeletal system morphogenesis / ureteric bud development / positive regulation of vascular endothelial cell proliferation / positive regulation of mesenchymal cell proliferation / cardiac muscle cell proliferation / inner ear morphogenesis / midbrain development / fibroblast growth factor binding / positive regulation of stem cell proliferation / Formation of paraxial mesoderm / regulation of cell differentiation / PI-3K cascade:FGFR1 / PI3K Cascade / epithelial to mesenchymal transition / positive regulation of blood vessel endothelial cell migration / fibroblast growth factor receptor signaling pathway / calcium ion homeostasis / chondrocyte differentiation / positive regulation of phospholipase C activity / SHC-mediated cascade:FGFR1 / cell maturation / positive regulation of cardiac muscle cell proliferation / FRS-mediated FGFR1 signaling / positive regulation of neuron differentiation / Signaling by FGFR1 in disease / NCAM signaling for neurite out-growth / SH2 domain binding / Signal transduction by L1 / skeletal system development / stem cell proliferation / stem cell differentiation / positive regulation of cell differentiation / sensory perception of sound / Negative regulation of FGFR1 signaling / neuron migration / positive regulation of MAP kinase activity / positive regulation of neuron projection development / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / neuron projection development / cell surface receptor protein tyrosine kinase signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / MAPK cascade / cell migration / PIP3 activates AKT signaling / heparin binding / gene expression / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / cytoplasmic vesicle / RAF/MAP kinase cascade / angiogenesis / protein tyrosine kinase activity / 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 | HOMO SAPIENS (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.957 Å | |||||||||
Authors | Bunney, T.D. / Wan, S. / Thiyagarajan, N. / Sutto, L. / Williams, S.V. / Ashford, P. / Koss, H. / Knowles, M.A. / Gervasio, F.L. / Coveney, P.V. / Katan, M. | |||||||||
Citation | Journal: Ebiomedicine / Year: 2015 Title: The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study Authors: Bunney, T. / Wan, S. / Thiyagarajan, N. / Sutto, L. / Williams, S.V. / Ashford, P. / Koss, H. / Knowles, M.A. / Gervasio, F.L. / Coveney, P.V. / Katan, M. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5am7.cif.gz | 253.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5am7.ent.gz | 204.9 KB | Display | PDB format |
PDBx/mmJSON format | 5am7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/am/5am7 ftp://data.pdbj.org/pub/pdb/validation_reports/am/5am7 | HTTPS FTP |
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-Related structure data
Related structure data | 4uwySC 5am6C C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 35340.680 Da / Num. of mol.: 2 / Fragment: KINASE DOMAIN, UNP RESIDUES 458-765 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PJ821 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): C41 LAMBDA 37 References: UniProt: P11362, receptor protein-tyrosine kinase #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.74 Å3/Da / Density % sol: 56 % / Description: NONE |
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Crystal grow | pH: 8 Details: 20 % PEG 5K MME, 0.1 M TRIS, PH 7.5, 0.2 M (NH4)2SO4 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9795 |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 8, 2014 / Details: MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.96→28.92 Å / Num. obs: 45034 / % possible obs: 83.2 % / Observed criterion σ(I): 0 / Redundancy: 3.8 % / Biso Wilson estimate: 31.05 Å2 / Rmerge(I) obs: 0.05 / Net I/σ(I): 13 |
Reflection shell | Resolution: 1.96→2 Å / Redundancy: 2 % / Rmerge(I) obs: 0.32 / Mean I/σ(I) obs: 1.9 / % possible all: 29.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 4UWY Resolution: 1.957→28.917 Å / SU ML: 0.25 / σ(F): 1.33 / Phase error: 31.92 / 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.957→28.917 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 226.9365 Å / Origin y: -11.1503 Å / Origin z: 28.711 Å
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Refinement TLS group | Selection details: ALL |