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Yorodumi- PDB-1wbv: Identification of novel p38 alpha MAP Kinase inhibitors using fra... -
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-Basic information
Entry | Database: PDB / ID: 1wbv | ||||||
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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 / SYNCHROTRON / OTHER / Resolution: 2 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.L. / 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.C. / Davis, D. ...Authors: Gill, A.L. / 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.C. / Davis, D.J. / Curry, J. / Anthony, R. / Padova, A. / Murray, C.W. / Carr, R.A. / Jhoti, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1wbv.cif.gz | 98.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1wbv.ent.gz | 75.4 KB | Display | PDB format |
PDBx/mmJSON format | 1wbv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1wbv_validation.pdf.gz | 480.9 KB | Display | wwPDB validaton report |
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Full document | 1wbv_full_validation.pdf.gz | 484.6 KB | Display | |
Data in XML | 1wbv_validation.xml.gz | 8.6 KB | Display | |
Data in CIF | 1wbv_validation.cif.gz | 15.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wb/1wbv ftp://data.pdbj.org/pub/pdb/validation_reports/wb/1wbv | HTTPS FTP |
-Related structure data
Related structure data | 1w82C 1w83C 1w84C 1wbnC 1wbsC 1wbtC 1wbwC 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-LI3 / | ||||||
#3: Chemical | #4: Chemical | ChemComp-DMS / | #5: 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: 3.03 Å3/Da / Density % sol: 59.11 % |
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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: SYNCHROTRON / Site: ESRF / Beamline: ID14-1 / Wavelength: 0.933 |
Detector | Type: ADSC CCD / Detector: CCD |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.933 Å / Relative weight: 1 |
Reflection | Resolution: 2→70.71 Å / Num. obs: 34365 / % possible obs: 93.7 % / Observed criterion σ(I): 2 / Redundancy: 2.5 % / Biso Wilson estimate: 28.3 Å2 / Rmerge(I) obs: 0.04 / Net I/σ(I): 7.1 |
-Processing
Software |
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Refinement | Method to determine structure: OTHER / Resolution: 2→70.71 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.923 / SU B: 3.562 / SU ML: 0.103 / Cross valid method: THROUGHOUT / ESU R: 0.169 / ESU R Free: 0.165 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.DISORDERED REGIONS AT A35, A170-A175
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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: 26.69 Å2
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Refinement step | Cycle: LAST / Resolution: 2→70.71 Å
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