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Yorodumi- PDB-1wbw: Identification of novel p38 alpha MAP Kinase inhibitors using fra... -
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-Basic information
Entry | Database: PDB / ID: 1wbw | ||||||
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Title | Identification of novel p38 alpha MAP Kinase inhibitors using fragment-based lead generation. | ||||||
Components | MITOGEN-ACTIVATED PROTEIN KINASE 14 | ||||||
Keywords | TRANSFERASE / P38 / MAP KINASE / INHIBITOR STRUCTURE / ALTERNATIVE SPLICING / ATP-BINDING / NUCLEAR PROTEIN / PHOSPHORYLATION / 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 / 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 / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / Activation of the AP-1 family of transcription factors / negative regulation of hippo signaling / 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 muramyl dipeptide / response to dietary excess / 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 / placenta development / activated TAK1 mediates p38 MAPK activation / positive regulation of glucose import / stem cell differentiation / cellular response to ionizing radiation / NOD1/2 Signaling Pathway / response to insulin / bone development / negative regulation of canonical Wnt signaling pathway / cell morphogenesis / cellular senescence / platelet activation / cellular response to virus / spindle pole / VEGFA-VEGFR2 Pathway / 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 response to tumor necrosis factor / peptidyl-serine phosphorylation / protein phosphatase binding / Regulation of TP53 Activity through Phosphorylation / cellular response to lipopolysaccharide / Oxidative Stress Induced Senescence / angiogenesis / secretory granule lumen / 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 / regulation of transcription by RNA polymerase II / Neutrophil degranulation / positive regulation of gene expression / apoptotic process / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding / nucleus Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / OTHER / Resolution: 2.41 Å | ||||||
Authors | Tickle, J. / Cleasby, A. / Devine, L.A. / Jhoti, H. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2005 Title: Identification of Novel P38Alpha Map Kinase Inhibitors Using Fragment-Based Lead Generation Authors: Gill, A. / Frederickson, M. / Cleasby, A. / Woodhead, S.J. / Carr, M.G. / Woodhead, A.J. / Walker, M.T. / Congreve, M.S. / Devine, L.A. / Tisi, D. / O'Reilly, M. / Seavers, L. / Davis, D.J. ...Authors: Gill, A. / Frederickson, M. / Cleasby, A. / Woodhead, S.J. / Carr, M.G. / Woodhead, A.J. / Walker, M.T. / Congreve, M.S. / Devine, L.A. / Tisi, D. / O'Reilly, M. / Seavers, L. / Davis, D.J. / Curry, J. / Anthony, R. / Padova, A. / Murray, C.W. / Carr, R.A.E. / Jhoti, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1wbw.cif.gz | 89.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1wbw.ent.gz | 68.1 KB | Display | PDB format |
PDBx/mmJSON format | 1wbw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1wbw_validation.pdf.gz | 440.5 KB | Display | wwPDB validaton report |
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Full document | 1wbw_full_validation.pdf.gz | 445.5 KB | Display | |
Data in XML | 1wbw_validation.xml.gz | 8.8 KB | Display | |
Data in CIF | 1wbw_validation.cif.gz | 14.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wb/1wbw ftp://data.pdbj.org/pub/pdb/validation_reports/wb/1wbw | HTTPS FTP |
-Related structure data
Related structure data | 1w82C 1w83C 1w84C 1wbnC 1wbsC 1wbtC 1wbvC C: citing same article (ref.) |
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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: 41343.195 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 1-360 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q16539, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-LI4 / |
#3: Water | ChemComp-HOH / |
Compound details | FUNCTION: RESPONDS TO ACTIVATION BY ENVIRONMENTAL STRESS, PRO-INFLAMMATORY CYTOKINES AND ...FUNCTION: RESPONDS TO ACTIVATION |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.05 Å3/Da / Density % sol: 59.38 % |
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Crystal grow | pH: 7 / Details: pH 7.00 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.54178 |
Detector | Type: MSC / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 2.41→29.11 Å / Num. obs: 18684 / % possible obs: 78.7 % / Observed criterion σ(I): 2 / Redundancy: 2 % / Biso Wilson estimate: 36.1 Å2 / Rmerge(I) obs: 0.13 / Net I/σ(I): 6.2 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER / Resolution: 2.41→29.11 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.875 / SU B: 8.844 / SU ML: 0.207 / Cross valid method: THROUGHOUT / ESU R: 0.372 / ESU R Free: 0.281 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. DISORDERED REGIONS ARE AT A14-A15,A35, A170- A175,A353-A354
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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: 25.2 Å2
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Refinement step | Cycle: LAST / Resolution: 2.41→29.11 Å
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