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Yorodumi- PDB-2zb0: Crystal structure of P38 in complex with biphenyl amide inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 2zb0 | ||||||
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Title | Crystal structure of P38 in complex with biphenyl amide inhibitor | ||||||
Components | Mitogen-activated protein kinase 14MAPK14 | ||||||
Keywords | TRANSFERASE / Serine/threonine protein kinase / map kinase / P38 / ATP-binding / Nucleotide-binding / Nucleus / Phosphorylation | ||||||
Function / homology | Function and homology information positive regulation of cyclase activity / 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 ...positive regulation of cyclase activity / 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 / stress-activated protein kinase signaling cascade / mitogen-activated protein kinase p38 binding / positive regulation of myoblast fusion / negative regulation of hippo signaling / positive regulation of muscle cell differentiation / 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 / regulation of ossification / MAP kinase activity / 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 / stress-activated MAPK cascade / skeletal muscle tissue development / signal transduction in response to DNA damage / 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 / placenta development / DNA damage checkpoint signaling / activated TAK1 mediates p38 MAPK activation / cellular response to ionizing radiation / stem cell differentiation / positive regulation of glucose import / response to insulin / NOD1/2 Signaling Pathway / bone development / cell morphogenesis / negative regulation of canonical Wnt signaling pathway / platelet activation / cellular response to virus / osteoblast differentiation / VEGFA-VEGFR2 Pathway / spindle pole / positive regulation of protein import into nucleus / 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 / angiogenesis / Oxidative Stress Induced Senescence / secretory granule lumen / cellular response to lipopolysaccharide / 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 / Resolution: 2.1 Å | ||||||
Authors | Somers, D.O. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2008 Title: Biphenyl amide p38 kinase inhibitors 1: Discovery and binding mode Authors: Angell, R.M. / Bamborough, P. / Cleasby, A. / Cockerill, S.G. / Jones, K.L. / Mooney, C.J. / Somers, D.O. / Walker, A.L. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2008 Title: Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR Authors: Angell, R.M. / Angell, T.D. / Bamborough, P. / Brown, D. / Brown, M. / Buckton, J.B. / Cockerill, S.G. / Edwards, C.D. / Jones, K.L. / Longstaff, T. / Smee, P.A. / Smith, K.J. / Somers, D.O. ...Authors: Angell, R.M. / Angell, T.D. / Bamborough, P. / Brown, D. / Brown, M. / Buckton, J.B. / Cockerill, S.G. / Edwards, C.D. / Jones, K.L. / Longstaff, T. / Smee, P.A. / Smith, K.J. / Somers, D.O. / Walker, A.L. / Willson, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2zb0.cif.gz | 89.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2zb0.ent.gz | 68.1 KB | Display | PDB format |
PDBx/mmJSON format | 2zb0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zb/2zb0 ftp://data.pdbj.org/pub/pdb/validation_reports/zb/2zb0 | HTTPS FTP |
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-Related 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: 41343.195 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: PRSETA / Production host: Escherichia coli (E. coli) / Strain (production host): BRL References: UniProt: Q16539, mitogen-activated protein kinase |
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#2: Chemical | ChemComp-GK3 / |
#3: Chemical | ChemComp-GOL / |
#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: 2.93 Å3/Da / Density % sol: 58.05 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH2R / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Aug 16, 2000 / Details: mirrors |
Radiation | Monochromator: Ni FILTER / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→35 Å / Num. obs: 28080 / % possible obs: 95.9 % / Biso Wilson estimate: 33.218 Å2 / Rmerge(I) obs: 0.076 / Χ2: 1.023 / Net I/σ(I): 12.9 |
Reflection shell | Resolution: 2.1→2.18 Å / Rmerge(I) obs: 0.465 / Mean I/σ(I) obs: 2.8 / Num. unique all: 2615 / Χ2: 1.071 / % possible all: 91.1 |
-Processing
Software |
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Refinement | Resolution: 2.1→20 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.946 / SU B: 7.782 / SU ML: 0.11 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.174 / ESU R Free: 0.155 / 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: 41.498 Å2
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Refinement step | Cycle: LAST / Resolution: 2.1→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.1→2.154 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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