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Yorodumi- PDB-4i0r: Crystal structure of spleen tyrosine kinase complexed with 2-(3,4... -
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-Basic information
Entry | Database: PDB / ID: 4i0r | ||||||
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Title | Crystal structure of spleen tyrosine kinase complexed with 2-(3,4,5-Trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide | ||||||
Components | Tyrosine-protein kinase SYK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / kinase inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information serotonin secretion by platelet / interleukin-15 receptor binding / positive regulation of interleukin-3 production / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / positive regulation of gamma-delta T cell differentiation / B cell receptor complex ...serotonin secretion by platelet / interleukin-15 receptor binding / positive regulation of interleukin-3 production / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / positive regulation of gamma-delta T cell differentiation / B cell receptor complex / neutrophil activation involved in immune response / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation / leukocyte activation involved in immune response / positive regulation of mast cell cytokine production / regulation of platelet activation / lymph vessel development / collagen-activated tyrosine kinase receptor signaling pathway / cell activation / positive regulation of mast cell degranulation / positive regulation of killing of cells of another organism / regulation of phagocytosis / beta selection / macrophage activation involved in immune response / leukotriene biosynthetic process / cellular response to molecule of fungal origin / FLT3 signaling through SRC family kinases / early phagosome / regulation of tumor necrosis factor-mediated signaling pathway / interleukin-3-mediated signaling pathway / cellular response to lipid / positive regulation of monocyte chemotactic protein-1 production / regulation of DNA-binding transcription factor activity / positive regulation of cell adhesion mediated by integrin / positive regulation of granulocyte macrophage colony-stimulating factor production / Fc epsilon receptor (FCERI) signaling / Interleukin-2 signaling / positive regulation of alpha-beta T cell differentiation / blood vessel morphogenesis / T cell receptor complex / positive regulation of B cell differentiation / leukocyte cell-cell adhesion / mast cell degranulation / Fc-gamma receptor signaling pathway involved in phagocytosis / positive regulation of interleukin-4 production / Dectin-2 family / Fc-epsilon receptor signaling pathway / stimulatory C-type lectin receptor signaling pathway / phospholipase binding / positive regulation of interleukin-10 production / positive regulation of receptor internalization / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / cellular response to low-density lipoprotein particle stimulus / FCGR activation / positive regulation of type I interferon production / phosphatase binding / positive regulation of bone resorption / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / positive regulation of calcium-mediated signaling / Signaling by CSF3 (G-CSF) / negative regulation of inflammatory response to antigenic stimulus / GPVI-mediated activation cascade / positive regulation of TORC1 signaling / positive regulation of interleukin-12 production / phosphotyrosine residue binding / SH2 domain binding / Integrin signaling / FCERI mediated Ca+2 mobilization / B cell differentiation / neutrophil chemotaxis / FCGR3A-mediated IL10 synthesis / regulation of ERK1 and ERK2 cascade / positive regulation of superoxide anion generation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / integrin-mediated signaling pathway / calcium-mediated signaling / positive regulation of interleukin-8 production / Regulation of signaling by CBL / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / cell surface receptor protein tyrosine kinase signaling pathway / animal organ morphogenesis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / positive regulation of protein-containing complex assembly / Inactivation of CSF3 (G-CSF) signaling / receptor internalization / Regulation of actin dynamics for phagocytic cup formation / platelet activation / CLEC7A (Dectin-1) signaling / peptidyl-tyrosine phosphorylation / protein import into nucleus / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / positive regulation of peptidyl-tyrosine phosphorylation / integrin binding / DAP12 signaling Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.1 Å | ||||||
Authors | Kuglstatter, A. / Villasenor, A.G. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors. Authors: Padilla, F. / Bhagirath, N. / Chen, S. / Chiao, E. / Goldstein, D.M. / Hermann, J.C. / Hsu, J. / Kennedy-Smith, J.J. / Kuglstatter, A. / Liao, C. / Liu, W. / Lowrie, L.E. / Luk, K.C. / ...Authors: Padilla, F. / Bhagirath, N. / Chen, S. / Chiao, E. / Goldstein, D.M. / Hermann, J.C. / Hsu, J. / Kennedy-Smith, J.J. / Kuglstatter, A. / Liao, C. / Liu, W. / Lowrie, L.E. / Luk, K.C. / Lynch, S.M. / Menke, J. / Niu, L. / Owens, T.D. / O-Yang, C. / Railkar, A. / Schoenfeld, R.C. / Slade, M. / Steiner, S. / Tan, Y.C. / Villasenor, A.G. / Wang, C. / Wanner, J. / Xie, W. / Xu, D. / Zhang, X. / Zhou, M. / Lucas, M.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4i0r.cif.gz | 125.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4i0r.ent.gz | 96.5 KB | Display | PDB format |
PDBx/mmJSON format | 4i0r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i0/4i0r ftp://data.pdbj.org/pub/pdb/validation_reports/i0/4i0r | HTTPS FTP |
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-Related structure data
Related structure data | 4i0sC 4i0tC 1xbbS 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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Unit cell |
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-Components
#1: Protein | Mass: 33884.004 Da / Num. of mol.: 1 / Fragment: protein kinase domain (UNP residues 356-635) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SYK / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF9 References: UniProt: P43405, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-1B4 / |
#3: 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: 2.25 Å3/Da / Density % sol: 45.4 % |
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Crystal grow | Temperature: 283 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 28% PEG4000, 0.2 M ammonium sulfate, 0.1 M HEPES, pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 283K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD |
Radiation | Monochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→45.08 Å / Num. obs: 18234 / % possible obs: 99 % / Redundancy: 4.9 % / Biso Wilson estimate: 39.4 Å2 / Rsym value: 0.055 / Net I/σ(I): 17.3 |
Reflection shell | Resolution: 2.1→2.18 Å / Redundancy: 3.9 % / Mean I/σ(I) obs: 1.9 / Num. unique all: 1710 / Rsym value: 0.513 / % possible all: 95.3 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 1XBB Resolution: 2.1→45.08 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.914 / SU B: 14.526 / SU ML: 0.174 / Cross valid method: THROUGHOUT / ESU R: 0.266 / ESU R Free: 0.212 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 49.59 Å2
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Refinement step | Cycle: LAST / Resolution: 2.1→45.08 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.1→2.156 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 3.6405 Å / Origin y: 10.7144 Å / Origin z: 20.2481 Å
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