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Yorodumi- PDB-3dpk: cFMS tyrosine kinase in complex with a pyridopyrimidinone inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 3dpk | ||||||
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Title | cFMS tyrosine kinase in complex with a pyridopyrimidinone inhibitor | ||||||
Components | Macrophage colony-stimulating factor 1 receptor, Fibroblast growth factor receptor 1 | ||||||
Keywords | TRANSFERASE / RECEPTOR TYROSINE KINASE / KINASE-INHIBITOR COMPLEX / ATP-binding / Glycoprotein / Immunoglobulin domain / Kinase / Membrane / Nucleotide-binding / Phosphoprotein / Proto-oncogene / Receptor / Transmembrane / Tyrosine-protein kinase / Craniosynostosis / Disease mutation / Dwarfism / Heparin-binding / Kallmann syndrome | ||||||
Function / homology | Function and homology information macrophage colony-stimulating factor receptor activity / forebrain neuron differentiation / CSF1-CSF1R complex / macrophage colony-stimulating factor signaling pathway / cell-cell junction maintenance / regulation of macrophage migration / 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 ...macrophage colony-stimulating factor receptor activity / forebrain neuron differentiation / CSF1-CSF1R complex / macrophage colony-stimulating factor signaling pathway / cell-cell junction maintenance / regulation of macrophage migration / 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 / cellular response to macrophage colony-stimulating factor stimulus / 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 / microglial cell proliferation / 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 / olfactory bulb development / FGFR1b ligand binding and activation / fibroblast growth factor receptor activity / branching involved in salivary gland morphogenesis / mammary gland duct 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 / positive regulation by host of viral process / ruffle organization / lung-associated mesenchyme development / cell projection assembly / cellular response to fibroblast growth factor stimulus / positive regulation of macrophage proliferation / outer ear morphogenesis / middle ear morphogenesis / positive regulation of cell motility / regulation of bone resorption / embryonic limb morphogenesis / skeletal system morphogenesis / positive regulation of endothelial cell chemotaxis / positive regulation of mesenchymal cell proliferation / cardiac muscle cell proliferation / positive regulation of vascular endothelial cell proliferation / ureteric bud development / inner ear morphogenesis / midbrain development / Other interleukin signaling / positive regulation of macrophage chemotaxis / fibroblast growth factor binding / cytokine binding / positive regulation of stem cell proliferation / Formation of paraxial mesoderm / PI-3K cascade:FGFR1 / regulation of cell differentiation / growth factor binding / cellular response to cytokine stimulus / phosphatidylinositol-mediated signaling / regulation of MAPK cascade / monocyte differentiation / hemopoiesis / macrophage differentiation / Transcriptional Regulation by VENTX / positive regulation of protein tyrosine kinase activity / 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 / : / SHC-mediated cascade:FGFR1 / positive regulation of chemokine production / cell maturation / positive regulation of tyrosine phosphorylation of STAT protein / 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 / osteoclast differentiation / Signal transduction by L1 / skeletal system development / stem cell proliferation / response to ischemia Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å | ||||||
Authors | Schubert, C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors Authors: Huang, H. / Hutta, D.A. / Rinker, J.M. / Hu, H. / Parsons, W.H. / Schubert, C. / DesJarlais, R.L. / Crysler, C.S. / Chaikin, M.A. / Donatelli, R.R. / Chen, Y. / Cheng, D. / Zhou, Z. / ...Authors: Huang, H. / Hutta, D.A. / Rinker, J.M. / Hu, H. / Parsons, W.H. / Schubert, C. / DesJarlais, R.L. / Crysler, C.S. / Chaikin, M.A. / Donatelli, R.R. / Chen, Y. / Cheng, D. / Zhou, Z. / Yurkow, E. / Manthey, C.L. / Player, M.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3dpk.cif.gz | 122.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3dpk.ent.gz | 95.2 KB | Display | PDB format |
PDBx/mmJSON format | 3dpk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dp/3dpk ftp://data.pdbj.org/pub/pdb/validation_reports/dp/3dpk | HTTPS FTP |
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-Related structure data
Related structure data | 2i1mS 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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Unit cell |
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-Components
#1: Protein | Mass: 38064.477 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN Mutation: Native kinase insert domain replaced by FGF receptor kinase insert domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: CSF1R, FGFBR, FGFR1, FLG, FLT2, FMS, BFGFR, CEK, HBGFR Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P07333, UniProt: P11362, receptor protein-tyrosine kinase | ||||
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#2: Chemical | #3: Chemical | ChemComp-8C5 / | #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.41 Å3/Da / Density % sol: 48.94 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.2 Details: PEG 3350, SODIUM ACETATE, LI2SO4, pH 5.2, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 19, 2005 |
Radiation | Monochromator: SAGITALLY FOCUSED Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.8→50 Å / Num. all: 27585 / Num. obs: 27585 / % possible obs: 83.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Rmerge(I) obs: 0.093 / Net I/σ(I): 12.2 |
Reflection shell | Resolution: 1.8→1.86 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.276 / Mean I/σ(I) obs: 4.3 / Num. unique all: 3289 / % possible all: 99.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2i1m Resolution: 1.95→34.1 Å / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber Details: Isotropic B-factor refinement for non-hydrogen atoms. Hydrogens were assigned the B-factor of their "parent" atom and one B-factor for all hydrogens was refined, as implemented in phenix
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Displacement parameters | Biso mean: 28.61 Å2 | |||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.95→34.1 Å
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Refine LS restraints |
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