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Yorodumi- PDB-4fyn: Crystal structure of spleen tyrosine kinase complexed with 3-(8-{... -
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-Basic information
Entry | Database: PDB / ID: 4fyn | ||||||
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Title | Crystal structure of spleen tyrosine kinase complexed with 3-(8-{4-[Ethyl-(2-hydroxy-ethyl)-amino]-phenylamino}-imidazo[1,2-a]pyrazin-5-yl)-phenol | ||||||
Components | Tyrosine-protein kinase SYK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / kinase inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information interleukin-15 receptor binding / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / serotonin secretion by platelet / positive regulation of interleukin-3 production / positive regulation of gamma-delta T cell differentiation / B cell receptor complex ...interleukin-15 receptor binding / regulation of superoxide anion generation / regulation of neutrophil degranulation / regulation of arachidonic acid secretion / cellular response to lectin / gamma-delta T cell differentiation / serotonin secretion by platelet / positive regulation of interleukin-3 production / positive regulation of gamma-delta T cell differentiation / B cell receptor complex / Toll-like receptor binding / regulation of platelet aggregation / positive regulation of alpha-beta T cell proliferation / leukocyte activation involved in immune response / neutrophil activation involved in immune response / positive regulation of mast cell cytokine production / lymph vessel development / regulation of platelet activation / 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 / early phagosome / cellular response to molecule of fungal origin / FLT3 signaling through SRC family kinases / leukotriene biosynthetic process / regulation of tumor necrosis factor-mediated signaling pathway / cellular response to lipid / positive regulation of monocyte chemotactic protein-1 production / interleukin-3-mediated signaling pathway / regulation of DNA-binding transcription factor activity / positive regulation of cell adhesion mediated by integrin / Fc epsilon receptor (FCERI) signaling / Interleukin-2 signaling / positive regulation of granulocyte macrophage colony-stimulating factor production / blood vessel morphogenesis / positive regulation of alpha-beta T cell differentiation / 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 / stimulatory C-type lectin receptor signaling pathway / Fc-epsilon receptor signaling pathway / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / phospholipase binding / positive regulation of receptor internalization / positive regulation of interleukin-10 production / 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 / cell surface receptor protein tyrosine kinase signaling pathway / positive regulation of interleukin-12 production / phosphotyrosine residue binding / Integrin signaling / SH2 domain binding / FCERI mediated Ca+2 mobilization / B cell differentiation / FCGR3A-mediated IL10 synthesis / neutrophil chemotaxis / regulation of ERK1 and ERK2 cascade / positive regulation of superoxide anion generation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / positive regulation of interleukin-8 production / integrin-mediated signaling pathway / Regulation of signaling by CBL / calcium-mediated signaling / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / 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 / platelet activation / Regulation of actin dynamics for phagocytic cup formation / 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: 2.318 Å | ||||||
Authors | Kuglstatter, A. / Villasenor, A.G. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2012 Title: Rational design of highly selective spleen tyrosine kinase inhibitors. Authors: Lucas, M.C. / Goldstein, D.M. / Hermann, J.C. / Kuglstatter, A. / Liu, W. / Luk, K.C. / Padilla, F. / Slade, M. / Villasenor, A.G. / Wanner, J. / Xie, W. / Zhang, X. / Liao, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4fyn.cif.gz | 126 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4fyn.ent.gz | 97.1 KB | Display | PDB format |
PDBx/mmJSON format | 4fyn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4fyn_validation.pdf.gz | 659.7 KB | Display | wwPDB validaton report |
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Full document | 4fyn_full_validation.pdf.gz | 662.7 KB | Display | |
Data in XML | 4fyn_validation.xml.gz | 12.3 KB | Display | |
Data in CIF | 4fyn_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fy/4fyn ftp://data.pdbj.org/pub/pdb/validation_reports/fy/4fyn | HTTPS FTP |
-Related structure data
Related structure data | 4fyoC 4fz6C 3fqeS S: Starting model for refinement C: citing same article (ref.) |
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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: RESIDUES 356-635, PROTEIN KINASE DOMAIN 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-0VE / |
#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: 2.28 Å3/Da / Density % sol: 45.99 % |
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Crystal grow | Temperature: 283 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 28% PEG 4000, 0.2M ammonium sulfate, 0.1M 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: SSRL / Beamline: BL9-2 / Wavelength: 0.97946 Å |
Detector | Type: MARMOSAIC 325 mm CCD / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97946 Å / Relative weight: 1 |
Reflection | Resolution: 2.3→50 Å / Num. all: 14003 / Num. obs: 12188 / % possible obs: 87.1 % / Redundancy: 5.4 % / Biso Wilson estimate: 42.6 Å2 / Rsym value: 0.18 / Net I/σ(I): 6.9 |
Reflection shell | Resolution: 2.3→2.38 Å / Redundancy: 3.7 % / Mean I/σ(I) obs: 1.7 / Num. unique all: 722 / Rsym value: 0.574 / % possible all: 62 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 3FQE Resolution: 2.318→45.36 Å / Cor.coef. Fo:Fc: 0.936 / Cor.coef. Fo:Fc free: 0.92 / SU B: 20.825 / SU ML: 0.223 / Cross valid method: THROUGHOUT / ESU R: 0.531 / ESU R Free: 0.295 / 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: 57.843 Å2
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Refinement step | Cycle: LAST / Resolution: 2.318→45.36 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.318→2.378 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 3.6827 Å / Origin y: 10.5266 Å / Origin z: 19.9581 Å
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Refinement TLS group |
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