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Yorodumi- PDB-3fmk: P38 kinase crystal structure in complex with 6-(2,4-Difluoro-phen... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3fmk | ||||||
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Title | P38 kinase crystal structure in complex with 6-(2,4-Difluoro-phenoxy)-8-methyl-2-((S)-1-methyl-2-tetrazol-2-yl-ethylamino)-8H-pyrido[2,3-d]pyrimidin-7-one | ||||||
Components | Mitogen-activated protein kinase 14 | ||||||
Keywords | SIGNALING PROTEIN / TRANSFERASE / P38 / MAP KINASE / SERINE/THREONINE KINASE / ATP-binding / Kinase / 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 / cartilage condensation ...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 / cartilage condensation / DSCAM interactions / positive regulation of myoblast fusion / cellular response to UV-B / Platelet sensitization by LDL / mitogen-activated protein kinase p38 binding / 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 / regulation of cytokine production involved in inflammatory response / ERK/MAPK targets / 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 / cellular response to vascular endothelial growth factor stimulus / mitogen-activated protein kinase / signal transduction in response to DNA damage / positive regulation of myoblast differentiation / chondrocyte differentiation / vascular endothelial growth factor receptor signaling pathway / stress-activated MAPK cascade / skeletal muscle tissue development / positive regulation of cardiac muscle cell proliferation / lipopolysaccharide-mediated signaling pathway / negative regulation of inflammatory response to antigenic stimulus / p38MAPK events / striated muscle cell differentiation / response to muscle stretch / positive regulation of interleukin-12 production / positive regulation of brown fat cell differentiation / 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 / NOD1/2 Signaling Pathway / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / placenta development / 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 / chemotaxis / positive regulation of reactive oxygen species metabolic process / cellular senescence / cellular response to tumor necrosis factor / peptidyl-serine phosphorylation / cellular response to lipopolysaccharide / protein phosphatase binding / angiogenesis / secretory granule lumen / Oxidative Stress Induced Senescence / Regulation of TP53 Activity through Phosphorylation / 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: 1.7 Å | ||||||
Authors | Kuglstatter, A. / Ghate, M. | ||||||
Citation | Journal: To be Published Title: The Discovery of Pamapimod and R1487 as Orally Bioavailable and Highly Selective Inhibitors of p38 Map Kinase Authors: Soth, M. / Kuglstatter, A. / Goldstein, D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3fmk.cif.gz | 92.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3fmk.ent.gz | 68.3 KB | Display | PDB format |
PDBx/mmJSON format | 3fmk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3fmk_validation.pdf.gz | 734.7 KB | Display | wwPDB validaton report |
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Full document | 3fmk_full_validation.pdf.gz | 738.4 KB | Display | |
Data in XML | 3fmk_validation.xml.gz | 18.5 KB | Display | |
Data in CIF | 3fmk_validation.cif.gz | 28.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fm/3fmk ftp://data.pdbj.org/pub/pdb/validation_reports/fm/3fmk | HTTPS FTP |
-Related structure data
Related structure data | 3flzC 3fmhC 3fmjC 3fsfC 1p38 C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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-Components
#1: Protein | Mass: 42748.715 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CSBP, CSBP1, CSBP2, CSPB1, MAPK14, MXI2 / Production host: ESCHERICHIA COLI (E. coli) References: UniProt: Q16539, mitogen-activated protein kinase |
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#2: Chemical | ChemComp-FMK / |
#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: 2.86 Å3/Da / Density % sol: 57 % |
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Crystal grow | Temperature: 290 K / Method: vapor diffusion, hanging drop / pH: 7.6 Details: 50 mM Hepes pH 7.6, 50 mM CaCl2, 17% PEG 3350, VAPOR DIFFUSION, HANGING DROP, temperature 290K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 210 / 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: 1.7→50 Å / Num. obs: 54575 / % possible obs: 99.9 % / Redundancy: 6.5 % / Biso Wilson estimate: 24.6 Å2 / Rsym value: 0.039 |
Reflection shell | Resolution: 1.7→1.76 Å / Redundancy: 6.5 % / Mean I/σ(I) obs: 3.2 / Num. unique all: 5365 / Rsym value: 0.558 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB entry 1P38 1p38 Resolution: 1.7→43.27 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.941 / SU B: 3.98 / SU ML: 0.06 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.101 / ESU R Free: 0.096 / 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: 25.13 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→43.27 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.747 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 21.3467 Å / Origin y: 17.3899 Å / Origin z: 21.7102 Å
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Refinement TLS group |
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