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Yorodumi- PDB-3fc1: Crystal structure of p38 kinase bound to pyrimido-pyridazinone in... -
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-Basic information
Entry | Database: PDB / ID: 3fc1 | ||||||
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Title | Crystal structure of p38 kinase bound to pyrimido-pyridazinone inhibitor | ||||||
Components | Mitogen-activated protein kinase 14MAPK14 | ||||||
Keywords | TRANSFERASE / kinase inhibitor / ATP-binding / Nucleotide-binding / Nucleus / Phosphoprotein / Serine/threonine-protein kinase | ||||||
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 / positive regulation of glucose import / placenta development / 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 / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Jacobs, M.D. / Bellon, S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2005 Title: Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase. Authors: Pearlman, D.A. #1: Journal: J.Med.Chem. / Year: 2001 Title: Are free energy calculations useful in practice? A comparison with rapid scoring functions for the p38 MAP kinase protein system. Authors: Pearlman, D.A. / Charifson, P.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3fc1.cif.gz | 83 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3fc1.ent.gz | 62.1 KB | Display | PDB format |
PDBx/mmJSON format | 3fc1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fc/3fc1 ftp://data.pdbj.org/pub/pdb/validation_reports/fc/3fc1 | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 41998.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 / Plasmid: pVL1392 (Pharmingen) / Production host: Trichoplusia ni (cabbage looper) / Tissue fraction (production host): insect cells / Variant (production host): Tn-368 References: UniProt: Q16539, mitogen-activated protein kinase |
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#2: Chemical | ChemComp-CL / |
#3: Chemical | ChemComp-52P / |
#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: 2.88 Å3/Da / Density % sol: 57.33 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 10 mg/mL Protein, 20 % PEG 3350, 0.1 M Tris-HCl pH 7.0, 50 mM MgCl2, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 110 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Mar 1, 1999 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→20 Å / Num. obs: 18713 / % possible obs: 95.2 % / Redundancy: 3 % / Rmerge(I) obs: 0.069 / Net I/σ(I): 8 |
Reflection shell | Resolution: 2.4→2.49 Å / Redundancy: 3 % / Rmerge(I) obs: 0.273 / Mean I/σ(I) obs: 3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→19.98 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.9 / SU B: 17.703 / SU ML: 0.183 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.36 / ESU R Free: 0.26 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: PDB entry 1WFC
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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: 34.826 Å2
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Refinement step | Cycle: LAST / Resolution: 2.4→19.98 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.4→2.461 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 44.2584 Å / Origin y: 25.7892 Å / Origin z: 40.5694 Å
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