+Open data
-Basic information
Entry | Database: PDB / ID: 4tyh | ||||||
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Title | Ternary complex of P38 and MK2 with a P38 inhibitor | ||||||
Components |
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Keywords | Transferase/Transferase inhibitor / P38 / MK2 / P38 inhibitor / Transferase-Transferase inhibitor complex | ||||||
Function / homology | Function and homology information macropinocytosis / CREB phosphorylation / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / DSCAM interactions / p38MAPK events / Activation of the AP-1 family of transcription factors / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / leukotriene metabolic process ...macropinocytosis / CREB phosphorylation / Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA / DSCAM interactions / p38MAPK events / Activation of the AP-1 family of transcription factors / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / Platelet sensitization by LDL / RHO GTPases Activate NADPH Oxidases / leukotriene metabolic process / ERK/MAPK targets / activated TAK1 mediates p38 MAPK activation / Synthesis of Leukotrienes (LT) and Eoxins (EX) / calcium-dependent protein serine/threonine kinase activity / NOD1/2 Signaling Pathway / ADP signalling through P2Y purinoceptor 1 / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / Myogenesis / regulation of tumor necrosis factor production / VEGFA-VEGFR2 Pathway / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of macrophage cytokine production / mitogen-activated protein kinase binding / regulation of interleukin-6 production / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / calcium/calmodulin-dependent protein kinase activity / 3'-UTR-mediated mRNA stabilization / toll-like receptor signaling pathway / cartilage condensation / cellular response to UV-B / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / glucose import / regulation of cytokine production involved in inflammatory response / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / response to dietary excess / response to muramyl dipeptide / inner ear development / Regulation of HSF1-mediated heat shock response / MAP kinase activity / regulation of ossification / mitogen-activated protein kinase / cellular response to vascular endothelial growth factor stimulus / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / regulation of cellular response to heat / stress-activated MAPK cascade / skeletal muscle tissue development / lipopolysaccharide-mediated signaling pathway / positive regulation of cardiac muscle cell proliferation / p38MAPK events / striated muscle cell differentiation / regulation of mRNA stability / response to muscle stretch / positive regulation of interleukin-12 production / positive regulation of brown fat cell differentiation / Neutrophil degranulation / osteoclast differentiation / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / response to cytokine / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / stem cell differentiation / positive regulation of glucose import / Regulation of TNFR1 signaling / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / placenta development / cell morphogenesis / cellular response to virus / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / osteoblast differentiation / glucose metabolic process / positive regulation of tumor necrosis factor production / positive regulation of reactive oxygen species metabolic process / MAPK cascade / kinase activity / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / peptidyl-serine phosphorylation / protein phosphatase binding / angiogenesis / Oxidative Stress Induced Senescence / transcription by RNA polymerase II / response to lipopolysaccharide / non-specific serine/threonine protein kinase / calmodulin binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 3 Å | ||||||
Authors | Cumming, J.G. / Debreczeni, J.E. / Edfeldt, F. / Evertsson, F. / Harrison, M. / Holdgate, G. / James, M. / Lamont, S. / Oldham, K. / Sullivan, J.E. / Wells, S. | ||||||
Citation | Journal: To Be Published Title: Discovery of substrate selective, ATP-competitive P38 alpha MAP kinase inhibitors Authors: Cumming, J.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4tyh.cif.gz | 280.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4tyh.ent.gz | 227.3 KB | Display | PDB format |
PDBx/mmJSON format | 4tyh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4tyh_validation.pdf.gz | 719.8 KB | Display | wwPDB validaton report |
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Full document | 4tyh_full_validation.pdf.gz | 732.9 KB | Display | |
Data in XML | 4tyh_validation.xml.gz | 25.6 KB | Display | |
Data in CIF | 4tyh_validation.cif.gz | 35 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ty/4tyh ftp://data.pdbj.org/pub/pdb/validation_reports/ty/4tyh | HTTPS FTP |
-Related structure data
Related structure data | 4tyk |
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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: 40385.805 Da / Num. of mol.: 1 / Fragment: UNP residues 51-400 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPKAPK2 / Production host: Escherichia coli (E. coli) References: UniProt: P49137, non-specific serine/threonine protein kinase |
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#2: Protein | Mass: 39856.621 Da / Num. of mol.: 1 / Fragment: UNP residues 6-353 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Mapk14, Crk1, Csbp1, Csbp2 / Production host: Escherichia coli (E. coli) References: UniProt: P47811, mitogen-activated protein kinase |
#3: Chemical | ChemComp-39G / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 2.86 Å3/Da / Density % sol: 56.95 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion / Details: 9% PEG 4K, 100mM NaCit, pH 5.6 / PH range: 5.6 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.987 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 14, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.987 Å / Relative weight: 1 |
Reflection | Resolution: 3→100 Å / Num. obs: 18845 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 7.86 % / Rmerge(I) obs: 0.2 / Net I/σ(I): 5.7 |
Reflection shell | Resolution: 3→3.11 Å / Redundancy: 7.94 % / Rmerge(I) obs: 0.66 / Mean I/σ(I) obs: 2 / % possible all: 100 |
-Processing
Software | Name: REFMAC / Version: 5.5.0090 / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Refinement | Resolution: 3→43.85 Å / Cor.coef. Fo:Fc: 0.915 / Cor.coef. Fo:Fc free: 0.873 / SU B: 53.929 / SU ML: 0.439 / Cross valid method: THROUGHOUT / ESU R Free: 0.528 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.081 Å2
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Refinement step | Cycle: 1 / Resolution: 3→43.85 Å
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