+Open data
-Basic information
Entry | Database: PDB / ID: 2i0h | ||||||
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Title | The structure of p38alpha in complex with an arylpyridazinone | ||||||
Components | Mitogen-activated protein kinase 14MAPK14 | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE KINASE / inhibitor design | ||||||
Function / homology | Function and homology information positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions ...positive regulation of cyclase activity / stress-activated protein kinase signaling cascade / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / CD163 mediating an anti-inflammatory response / regulation of synaptic membrane adhesion / stress-induced premature senescence / cell surface receptor protein serine/threonine kinase signaling pathway / 3'-UTR-mediated mRNA stabilization / KSRP (KHSRP) binds and destabilizes mRNA / DSCAM interactions / cartilage condensation / cellular response to UV-B / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / positive regulation of muscle cell differentiation / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / Activation of the AP-1 family of transcription factors / ERK/MAPK targets / regulation of cytokine production involved in inflammatory response / p38MAPK cascade / fatty acid oxidation / cellular response to lipoteichoic acid / MAP kinase kinase activity / response to dietary excess / response to muramyl dipeptide / RHO GTPases Activate NADPH Oxidases / MAP kinase activity / regulation of ossification / mitogen-activated protein kinase / cellular response to vascular endothelial growth factor stimulus / positive regulation of myoblast differentiation / signal transduction in response to DNA damage / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / lipopolysaccharide-mediated signaling pathway / positive regulation of cardiac muscle cell proliferation / negative regulation of inflammatory response to antigenic stimulus / p38MAPK events / striated muscle cell differentiation / response to muscle stretch / positive regulation of brown fat cell differentiation / positive regulation of interleukin-12 production / osteoclast differentiation / positive regulation of erythrocyte differentiation / DNA damage checkpoint signaling / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / stem cell differentiation / placenta development / positive regulation of glucose import / NOD1/2 Signaling Pathway / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / platelet activation / cellular response to virus / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / osteoblast differentiation / ADP signalling through P2Y purinoceptor 1 / glucose metabolic process / positive regulation of reactive oxygen species metabolic process / chemotaxis / cellular senescence / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / protein phosphatase binding / secretory granule lumen / Oxidative Stress Induced Senescence / angiogenesis / Regulation of TP53 Activity through Phosphorylation / cellular response to lipopolysaccharide / ficolin-1-rich granule lumen / transcription by RNA polymerase II / cell surface receptor signaling pathway / intracellular signal transduction / nuclear speck / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / apoptotic process / Neutrophil degranulation / positive regulation of gene expression / regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2 Å | ||||||
Authors | Natarajan, S.R. / Heller, S.T. / Nam, K. / Singh, S.B. / Scapin, G. / Patel, S. / Thompson, J.E. / Fitzgerald, C.E. / O'Keefe, S.J. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2006 Title: p38 MAP Kinase Inhibitors Part 6: 2-Arylpyridazin-3-ones as templates for inhibitor design. Authors: Natarajan, S.R. / Heller, S.T. / Nam, K. / Singh, S.B. / Scapin, G. / Patel, S. / Fitzgerald, C.E. / Thompson, J.E. / O'Keefe, S.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2i0h.cif.gz | 97.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2i0h.ent.gz | 72.2 KB | Display | PDB format |
PDBx/mmJSON format | 2i0h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/i0/2i0h ftp://data.pdbj.org/pub/pdb/validation_reports/i0/2i0h | HTTPS FTP |
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-Related structure data
Related structure data | 1wfcS 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: 41982.871 Da / Num. of mol.: 1 / Mutation: C162S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14, CSBP, CSBP1, CSBP2, MXI2 / Plasmid: PET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) References: UniProt: Q16539, mitogen-activated protein kinase | ||||
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#2: Chemical | #3: Chemical | #4: 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: 2.85 Å3/Da / Density % sol: 56.88 % |
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Crystal grow | Temperature: 284 K / Method: vapor diffusion, hanging drop / pH: 7 Details: SODIUM CITRATE, AMMONIUM SULFATE, HEPES, PH 7.00, VAPOR DIFFUSION, HANGING DROP, temperature 284K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-BM / Wavelength: 1 / Wavelength: 1 Å | |||||||||
Detector | Type: MARRESEARCH / Detector: CCD / Date: Dec 15, 2001 | |||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||
Radiation wavelength |
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Reflection | Resolution: 2→30 Å / Num. all: 33403 / Num. obs: 32668 / % possible obs: 97.8 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 6.6 % / Biso Wilson estimate: 19 Å2 / Rmerge(I) obs: 0.093 / Net I/σ(I): 4.9 | |||||||||
Reflection shell | Resolution: 2→2.07 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.367 / Mean I/σ(I) obs: 1.8 / Num. unique all: 3275 / % possible all: 87.7 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 1WFC Resolution: 2→30 Å / Isotropic thermal model: ANISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: MASK / Bsol: 41.96 Å2 / ksol: 0.36 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 21.4 Å2
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Refine analyze | Luzzati coordinate error obs: 0.2 Å / Luzzati d res low obs: 5 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.07 Å
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