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Yorodumi- PDB-3hrb: p38 kinase Crystal structure in complex with small molecule inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 3hrb | ||||||
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Title | p38 kinase Crystal structure in complex with small molecule inhibitor | ||||||
Components | Mitogen-activated protein kinase 14 | ||||||
Keywords | TRANSFERASE / p38 MAP KINASE / INHIBITOR COMPLEX / Alternative splicing / ATP-binding / Cytoplasm / Kinase / Nucleotide-binding / Nucleus / Phosphoprotein / Polymorphism / 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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.2 Å | ||||||
Authors | Segarra, V. / Lumeras, W. / Vidal, B. / Leonard, P. / Fisher, M. / Lamers, M. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: Design, synthesis, and structure-activity relationships of aminopyridine N-oxides, a novel scaffold for the potent and selective inhibition of p38 mitogen activated protein kinase Authors: Lumeras, W. / Caturla, F. / Vidal, L. / Esteve, C. / Balague, C. / Orellana, A. / Dominguez, M. / Roca, R. / Huerta, J.M. / Godessart, N. / Vidal, B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3hrb.cif.gz | 86.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3hrb.ent.gz | 63.4 KB | Display | PDB format |
PDBx/mmJSON format | 3hrb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3hrb_validation.pdf.gz | 736.8 KB | Display | wwPDB validaton report |
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Full document | 3hrb_full_validation.pdf.gz | 740.3 KB | Display | |
Data in XML | 3hrb_validation.xml.gz | 16.3 KB | Display | |
Data in CIF | 3hrb_validation.cif.gz | 23.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hr/3hrb ftp://data.pdbj.org/pub/pdb/validation_reports/hr/3hrb | HTTPS FTP |
-Related structure data
Related structure data | 1a9uS 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: 41212.000 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Description: The plasmid used is annotated as Sareum proprietary Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 / Production host: Escherichia coli (E. coli) References: UniProt: Q16539, mitogen-activated protein kinase |
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#2: Chemical | ChemComp-I39 / [ |
#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: 2.91 Å3/Da / Density % sol: 57.73 % / Mosaicity: 0.54 ° |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 22% PEG 3350, 0.2M NaCl, 0.1M Bis-Tris pH 6.5, 1mM THP, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU / Detector: IMAGE PLATE / Date: Jun 23, 2005 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→70.744 Å / Num. all: 40419 / Num. obs: 20806 / % possible obs: 84.2 % / Redundancy: 1.9 % / Biso Wilson estimate: 35.9 Å2 / Rmerge(I) obs: 0.057 / Rsym value: 0.057 / Net I/σ(I): 9.5 |
Reflection shell | Resolution: 2.2→2.32 Å / Redundancy: 1.8 % / Rmerge(I) obs: 0.367 / Mean I/σ(I) obs: 2.2 / Num. unique all: 5586 / Rsym value: 0.367 / % possible all: 89.1 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1A9U Resolution: 2.2→29.7 Å / Occupancy max: 1 / Occupancy min: 1 / FOM work R set: 0.812 / SU B: 6.386 / SU ML: 0.158 / SU R Cruickshank DPI: 0.315 / SU Rfree: 0.241 / Cross valid method: THROUGHOUT / ESU R: 0.315 / ESU R Free: 0.241
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Displacement parameters | Biso max: 65.17 Å2 / Biso mean: 26.83 Å2 / Biso min: 10.45 Å2
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Refinement step | Cycle: LAST / Resolution: 2.2→29.7 Å
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Refine LS restraints |
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