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Yorodumi- PDB-1ouy: The structure of p38 alpha in complex with a dihydropyrido-pyrimi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1ouy | ||||||
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Title | The structure of p38 alpha in complex with a dihydropyrido-pyrimidine inhibitor | ||||||
Components | Mitogen-activated protein kinase 14MAPK14 | ||||||
Keywords | TRANSFERASE / MAP kinase / hydrophobic pocket / kinase domain / ATP binding domain | ||||||
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 / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.5 Å | ||||||
Authors | Fitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G. | ||||||
Citation | Journal: Nat.Struct.Biol. / Year: 2003 Title: Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity Authors: Fitzgerald, C.E. / Patel, S.B. / Becker, J.W. / Cameron, P.M. / Zaller, D. / Pikounis, V.B. / O'Keefe, S.J. / Scapin, G. #1: Journal: Bioorg.Med.Chem.Lett. / Year: 2003 Title: p38MAP kinase inhibitors part 1: Design and development of a new class of potent and highly selective inhibitors based on 3,4-dihydropyrido[3,2-d]pyrimidone scaffold Authors: Natarajan, S.R. / Wisnoski, D.D. / Singh, S.B. / Stelmach, J.E. / O'Neill, E.A. / Schwartz, C.D. / Thompson, C.M. / Fitzgerald, C.E. / O'keefe, S.J. / Kumar, S. / Hop, C.E. / Zaller, D.M. / ...Authors: Natarajan, S.R. / Wisnoski, D.D. / Singh, S.B. / Stelmach, J.E. / O'Neill, E.A. / Schwartz, C.D. / Thompson, C.M. / Fitzgerald, C.E. / O'keefe, S.J. / Kumar, S. / Hop, C.E. / Zaller, D.M. / Schmatz, D.M. / Doherty, J.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1ouy.cif.gz | 85.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1ouy.ent.gz | 63.5 KB | Display | PDB format |
PDBx/mmJSON format | 1ouy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ou/1ouy ftp://data.pdbj.org/pub/pdb/validation_reports/ou/1ouy | HTTPS FTP |
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-Related structure data
Related structure data | 1oukSC 1oveC S: Starting model for refinement 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: 41998.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14 / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q16539, EC: 2.7.1.37 |
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#2: Chemical | ChemComp-094 / |
#3: 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: 3.07 Å3/Da / Density % sol: 59.59 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7 Details: Sodium citrate, Ammonium sulfate, HEPES buffer, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS pH: 7.5 / Method: vapor diffusion / Details: Wilson, K.P., (1996) J.Biol.Chem., 271, 27696. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: MARRESEARCH / Detector: CCD / Date: Sep 15, 2000 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→15 Å / Num. all: 18037 / Num. obs: 17975 / % possible obs: 99.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.4 % / Biso Wilson estimate: 47.5 Å2 / Rsym value: 0.098 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 2.5→2.6 Å / Redundancy: 5.9 % / Mean I/σ(I) obs: 1.6 / Num. unique all: 2949 / Rsym value: 0.347 / % possible all: 99.6 |
Reflection | *PLUS Rmerge(I) obs: 0.098 |
Reflection shell | *PLUS % possible obs: 99.6 % / Num. unique obs: 2937 / Rmerge(I) obs: 0.347 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 1OUK Resolution: 2.5→15 Å / Isotropic thermal model: Anisotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber / Details: as implemented in CNX
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Solvent computation | Solvent model: MASK / Bsol: 30.95 Å2 / ksol: 0.338 e/Å3 | |||||||||||||||||||||||||
Displacement parameters | Biso mean: 40.8 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.5→15 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.6 Å
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Refinement | *PLUS Lowest resolution: 15 Å | |||||||||||||||||||||||||
Solvent computation | *PLUS | |||||||||||||||||||||||||
Displacement parameters | *PLUS | |||||||||||||||||||||||||
Refine LS restraints | *PLUS
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