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- PDB-3krj: cFMS tyrosine kinase in complex with 4-Cyano-1H-imidazole-2-carbo... -
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Open data
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Basic information
Entry | Database: PDB / ID: 3krj | ||||||
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Title | cFMS tyrosine kinase in complex with 4-Cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide | ||||||
![]() | Macrophage colony-stimulating factor 1 receptor, Basic fibroblast growth factor receptor 1 | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / Kinase / inhibitor / chimera / ATP-binding / Disulfide bond / Glycoprotein / Immunoglobulin domain / Membrane / Nucleotide-binding / Phosphoprotein / Proto-oncogene / Receptor / Transferase / Transmembrane / Tyrosine-protein kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() 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 / cellular response to macrophage colony-stimulating factor stimulus / 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 / microglial cell proliferation / 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 / mammary gland duct morphogenesis / 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 / positive regulation by host of viral process / lung-associated mesenchyme development / ruffle organization / cell projection assembly / cellular response to fibroblast growth factor stimulus / positive regulation of macrophage proliferation / outer ear morphogenesis / regulation of bone resorption / positive regulation of cell motility / 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 / Other interleukin signaling / positive regulation of macrophage chemotaxis / regulation of cell differentiation / positive regulation of stem cell proliferation / fibroblast growth factor binding / Formation of paraxial mesoderm / PI-3K cascade:FGFR1 / growth factor binding / cellular response to cytokine stimulus / cytokine binding / phosphatidylinositol-mediated signaling / monocyte differentiation / regulation of MAPK cascade / macrophage differentiation / hemopoiesis / positive regulation of protein tyrosine kinase activity / Transcriptional Regulation by VENTX / 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 chemokine production / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of cardiac muscle cell proliferation / cell maturation / cell surface receptor protein tyrosine kinase signaling pathway / FRS-mediated FGFR1 signaling / Signaling by FGFR1 in disease / positive regulation of neuron differentiation / NCAM signaling for neurite out-growth / SH2 domain binding / osteoclast differentiation / stem cell proliferation / Signal transduction by L1 / skeletal system development Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Schubert, C. | ||||||
![]() | ![]() Title: Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-N-[2-(1-cyclohexen-1-yl)-4-[1- ...Title: Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141). Authors: Illig, C.R. / Manthey, C.L. / Wall, M.J. / Meegalla, S.K. / Chen, J. / Wilson, K.J. / Ballentine, S.K. / Desjarlais, R.L. / Schubert, C. / Crysler, C.S. / Chen, Y. / Molloy, C.J. / Chaikin, ...Authors: Illig, C.R. / Manthey, C.L. / Wall, M.J. / Meegalla, S.K. / Chen, J. / Wilson, K.J. / Ballentine, S.K. / Desjarlais, R.L. / Schubert, C. / Crysler, C.S. / Chen, Y. / Molloy, C.J. / Chaikin, M.A. / Donatelli, R.R. / Yurkow, E. / Zhou, Z. / Player, M.R. / Tomczuk, B.E. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 191.2 KB | Display | ![]() |
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PDB format | ![]() | 153.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 3krlC ![]() 2i0vS C: citing same article ( 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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Unit cell |
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Components
#1: Protein | Mass: 38064.477 Da / Num. of mol.: 1 / Fragment: UNP residues 538-678, 753-922 / Mutation: C584S Source method: isolated from a genetically manipulated source Details: Native kinase insert domain of c-fms replaced by FGF receptor kinase insert domain Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P07333, UniProt: P11362, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-ACT / |
#3: Chemical | ChemComp-KRJ / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.51 Å3/Da / Density % sol: 50.94 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: 13-19%PRG3350 100mM NaAcetate, pH 5.6 200mM (NH4)2SO4, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: MAR CCD 165 mm / Detector: CCD / Date: May 1, 2004 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→16.4 Å / Num. obs: 21192 / % possible obs: 97.2 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.5 % / Rmerge(I) obs: 0.075 / Net I/σ(I): 15.3 |
Reflection shell | Resolution: 2.1→2.17 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.29 / Mean I/σ(I) obs: 4.1 / Num. unique all: 2181 / % possible all: 100 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: PDB entry 2i0v Resolution: 2.1→16.4 Å / SU ML: 0.36 / Isotropic thermal model: isotropic, TLS / Cross valid method: THROUGHOUT / σ(F): 0.07 / 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 / Bsol: 63.127 Å2 / ksol: 0.465 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.1→16.4 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group | Selection details: chain A and resid 869:912) |