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Yorodumi- PDB-3iph: Crystal structure of p38 in complex with a biphenylamide inhibitor -
+Open data
-Basic information
Entry | Database: PDB / ID: 3iph | ||||||
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Title | Crystal structure of p38 in complex with a biphenylamide inhibitor | ||||||
Components | Mitogen-activated protein kinase 14 | ||||||
Keywords | TRANSFERASE / P38 / SERINE/THREONINE PROTEIN KINASE / MAP 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 / FOURIER SYNTHESIS / Resolution: 2.1 Å | ||||||
Authors | Somers, D.O. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression. Authors: Aston, N.M. / Bamborough, P. / Buckton, J.B. / Edwards, C.D. / Holmes, D.S. / Jones, K.L. / Patel, V.K. / Smee, P.A. / Somers, D.O. / Vitulli, G. / Walker, A.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3iph.cif.gz | 93.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3iph.ent.gz | 70.2 KB | Display | PDB format |
PDBx/mmJSON format | 3iph.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3iph_validation.pdf.gz | 730.4 KB | Display | wwPDB validaton report |
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Full document | 3iph_full_validation.pdf.gz | 735.3 KB | Display | |
Data in XML | 3iph_validation.xml.gz | 19.4 KB | Display | |
Data in CIF | 3iph_validation.cif.gz | 28.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ip/3iph ftp://data.pdbj.org/pub/pdb/validation_reports/ip/3iph | HTTPS FTP |
-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: 41375.195 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: 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-G11 / | ||
#3: Chemical | ChemComp-SO4 / | ||
#4: Chemical | ChemComp-GOL / #5: 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: 2.97 Å3/Da / Density % sol: 58.53 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.5 Details: 0.1M ADA, 0.18M (NH4)2SO4, 18-20% PEG5000MME, 3-4% Jeffamine ED600, 2mM b-Mercaptoethanol. , pH 6.5, VAPOR DIFFUSION, 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: Nov 22, 2001 / 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: 25525 / % possible obs: 86.1 % / Biso Wilson estimate: 27.8 Å2 / Rmerge(I) obs: 0.102 / Χ2: 0.996 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 2.1→2.18 Å / Rmerge(I) obs: 0.542 / Num. unique all: 2513 / Χ2: 0.974 / % possible all: 86.1 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 1WFC Resolution: 2.1→20 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.919 / WRfactor Rfree: 0.234 / WRfactor Rwork: 0.167 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.823 / SU B: 9.89 / SU ML: 0.138 / SU R Cruickshank DPI: 0.206 / SU Rfree: 0.194 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.206 / ESU R Free: 0.194 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: U VALUES : RESIDUAL ONLY
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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 max: 74.55 Å2 / Biso mean: 35.344 Å2 / Biso min: 14.55 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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