+Open data
-Basic information
Entry | Database: PDB / ID: 4l02 | ||||||
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Title | Crystal Structure of SphK1 with inhibitor | ||||||
Components | Sphingosine kinase 1 | ||||||
Keywords | Transferase/Transferase Inhibitor / lipid kinase / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information sphingosine kinase / sphinganine kinase activity / D-erythro-sphingosine kinase activity / sphingoid catabolic process / regulation of endosomal vesicle fusion / sphingosine metabolic process / negative regulation of ceramide biosynthetic process / sphingosine-1-phosphate receptor activity / regulation of microglial cell activation / regulation of interleukin-1 beta production ...sphingosine kinase / sphinganine kinase activity / D-erythro-sphingosine kinase activity / sphingoid catabolic process / regulation of endosomal vesicle fusion / sphingosine metabolic process / negative regulation of ceramide biosynthetic process / sphingosine-1-phosphate receptor activity / regulation of microglial cell activation / regulation of interleukin-1 beta production / sphingosine biosynthetic process / sphingolipid biosynthetic process / regulation of neuroinflammatory response / Sphingolipid de novo biosynthesis / positive regulation of smooth muscle contraction / regulation of phagocytosis / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of p38MAPK cascade / DNA biosynthetic process / protein acetylation / blood vessel development / positive regulation of interleukin-17 production / Association of TriC/CCT with target proteins during biosynthesis / acetyltransferase activity / regulation of endocytosis / endocytic vesicle / cellular response to vascular endothelial growth factor stimulus / response to tumor necrosis factor / clathrin-coated pit / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / positive regulation of mitotic cell cycle / positive regulation of mitotic nuclear division / protein phosphatase 2A binding / positive regulation of peptidyl-threonine phosphorylation / VEGFR2 mediated cell proliferation / positive regulation of protein ubiquitination / calcium-mediated signaling / brain development / PKR-mediated signaling / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of angiogenesis / positive regulation of fibroblast proliferation / presynapse / positive regulation of NF-kappaB transcription factor activity / early endosome membrane / positive regulation of cell growth / cell population proliferation / Extra-nuclear estrogen signaling / calmodulin binding / intracellular signal transduction / positive regulation of cell migration / inflammatory response / phosphorylation / intracellular membrane-bounded organelle / lipid binding / negative regulation of apoptotic process / magnesium ion binding / DNA binding / nucleoplasm / ATP binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.75 Å | ||||||
Authors | Min, X. / Walker, N. / Wang, Z. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2013 Title: Structure guided design of a series of sphingosine kinase (SphK) inhibitors. Authors: Gustin, D.J. / Li, Y. / Brown, M.L. / Min, X. / Schmitt, M.J. / Wanska, M. / Wang, X. / Connors, R. / Johnstone, S. / Cardozo, M. / Cheng, A.C. / Jeffries, S. / Franks, B. / Li, S. / Shen, S. ...Authors: Gustin, D.J. / Li, Y. / Brown, M.L. / Min, X. / Schmitt, M.J. / Wanska, M. / Wang, X. / Connors, R. / Johnstone, S. / Cardozo, M. / Cheng, A.C. / Jeffries, S. / Franks, B. / Li, S. / Shen, S. / Wong, M. / Wesche, H. / Xu, G. / Carlson, T.J. / Plant, M. / Morgenstern, K. / Rex, K. / Schmitt, J. / Coxon, A. / Walker, N. / Kayser, F. / Wang, Z. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4l02.cif.gz | 210.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4l02.ent.gz | 171 KB | Display | PDB format |
PDBx/mmJSON format | 4l02.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l0/4l02 ftp://data.pdbj.org/pub/pdb/validation_reports/l0/4l02 | HTTPS FTP |
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-Related structure data
Related structure data | |
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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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3 |
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Unit cell |
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-Components
#1: Protein | Mass: 42891.625 Da / Num. of mol.: 3 / Fragment: UNP residues 9-364 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: Sphingosine kinase 1, SPHK, SPHK1, SPK / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): sf9 / References: UniProt: Q9NYA1, sphingosine kinase #2: Chemical | #3: 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: 2.39 Å3/Da / Density % sol: 48.6 % |
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Crystal grow | Temperature: 289 K / Method: vapor diffusion, sitting drop / pH: 6 Details: 1.0-1.4M AMMONIUM SULFATE, 0.3-1.3M NACL, 0.1M BIS-TRIS, pH 6.0, VAPOR DIFFUSION, SITTING DROP, temperature 289KK |
-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 | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.75→50 Å / Num. obs: 32431 / % possible obs: 99.94 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 4 % / Biso Wilson estimate: 42.36 Å2 / Rmerge(I) obs: 0.102 / Rsym value: 0.102 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 2.75→2.85 Å / Redundancy: 4 % / Rmerge(I) obs: 0.548 / Mean I/σ(I) obs: 3 / Rsym value: 0.548 / % possible all: 99.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.75→30 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.888 / SU B: 14.229 / SU ML: 0.285 / Cross valid method: THROUGHOUT / ESU R Free: 0.372 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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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: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 41.785 Å2
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Refinement step | Cycle: LAST / Resolution: 2.75→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.75→2.822 Å / Total num. of bins used: 20
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