+Open data
-Basic information
Entry | Database: PDB / ID: 4aa5 | ||||||
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Title | P38ALPHA MAP KINASE BOUND TO CMPD 33 | ||||||
Components | MITOGEN-ACTIVATED PROTEIN KINASE 14MAPK14 | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE KINASE | ||||||
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 / positive regulation of muscle cell differentiation / negative regulation of hippo signaling / positive regulation of myotube differentiation / NFAT protein binding / Myogenesis / glucose import / response to dietary excess / 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 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 / negative regulation of inflammatory response to antigenic stimulus / positive regulation of cardiac muscle cell proliferation / 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 / negative regulation of canonical Wnt signaling pathway / response to insulin / NOD1/2 Signaling Pathway / bone development / cell morphogenesis / platelet activation / osteoblast differentiation / cellular response to virus / 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 / protein phosphatase binding / peptidyl-serine phosphorylation / 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 / MOLECULAR REPLACEMENT / Resolution: 2.38 Å | ||||||
Authors | Gerhardt, S. / Hargreaves, D. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2012 Title: The Discovery of N-Cyclopropyl-4-Methyl-3-[6--(4-Methylpiperazin-1-Yl-4-Oxoquinazolin-3(4H)-Yl]Benzamide (Azd6703), a Clinical P38Alpha Map Kinase Inhibitor for the Treatment of Inflammatory Diseases Authors: Brown, D.S. / Cumming, J.G. / Bethel, P. / Finlayson, J. / Gerhardt, S. / Nash, I. / Pauptit, R. / Pike, K.G. / Reid, A. / Snelson, W. / Swallow, S. / Thompson, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4aa5.cif.gz | 146.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4aa5.ent.gz | 121.6 KB | Display | PDB format |
PDBx/mmJSON format | 4aa5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aa/4aa5 ftp://data.pdbj.org/pub/pdb/validation_reports/aa/4aa5 | 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: 42072.941 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PT7 3.3 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) References: UniProt: Q16539, mitogen-activated protein kinase, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-NQB / |
#3: Water | ChemComp-HOH / |
Sequence details | N-TERMINAL HEXA-HIS EXPRESSION |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.24 Å3/Da / Density % sol: 45.1 % / Description: NONE |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 6-10% PEG-MME 5000, PH 6.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 298K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: ENRAF-NONIUS FR591 / Wavelength: 1.5418 |
Detector | Type: MARRESEARCH / Detector: IMAGE PLATE / Date: Jan 7, 2003 / Details: MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.38→19.32 Å / Num. obs: 15291 / % possible obs: 95.5 % / Observed criterion σ(I): 0 / Redundancy: 3.6 % / Rmerge(I) obs: 0.05 / Net I/σ(I): 15 |
Reflection shell | Resolution: 2.38→2.51 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.28 / Mean I/σ(I) obs: 5.8 / % possible all: 90.3 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.38→19.32 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.905 / SU B: 20.054 / SU ML: 0.222 / Cross valid method: THROUGHOUT / ESU R: 0.568 / ESU R Free: 0.29 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. DISORDERED REGIONS WERE NOT MODELED IN THE FINAL STRUCTURE.
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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: 34.392 Å2
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Refinement step | Cycle: LAST / Resolution: 2.38→19.32 Å
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