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Yorodumi- PDB-1m7q: Crystal structure of p38 MAP kinase in complex with a dihydroquin... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1m7q | ||||||
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Title | Crystal structure of p38 MAP kinase in complex with a dihydroquinazolinone inhibitor | ||||||
Components | Mitogen-activated protein kinase 14 | ||||||
Keywords | TRANSFERASE / serine/threonine kinase / ATP-binding domain / inhibitor | ||||||
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 / FOURIER SYNTHESIS / Resolution: 2.4 Å | ||||||
Authors | Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E.C.A. / Wang, Z. / Cameron, P.M. / Nichols, E.A. ...Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E.C.A. / Wang, Z. / Cameron, P.M. / Nichols, E.A. / O'Keefe, S.J. / O'Neill, E.A. / Schmatz, D.M. / Schwartz, C.D. / Thompson, C.M. / Zaller, D.M. / Doherty, J.B. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2003 Title: Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase. Authors: Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E. / Wang, Z. / Strauss, J.R. / Cameron, P.M. / Nichols, E.A. / O'Keefe, S.J. / O'Neill, E.A. / ...Authors: Stelmach, J.E. / Liu, L. / Patel, S.B. / Pivnichny, J.V. / Scapin, G. / Singh, S. / Hop, C.E. / Wang, Z. / Strauss, J.R. / Cameron, P.M. / Nichols, E.A. / O'Keefe, S.J. / O'Neill, E.A. / Schmatz, D.M. / Schwartz, C.D. / Thompson, C.M. / Zaller, 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 | 1m7q.cif.gz | 85.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1m7q.ent.gz | 64.1 KB | Display | PDB format |
PDBx/mmJSON format | 1m7q.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m7/1m7q ftp://data.pdbj.org/pub/pdb/validation_reports/m7/1m7q | HTTPS FTP |
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-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: 41998.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) References: UniProt: Q16539, Transferases; Transferring phosphorus-containing groups; Phosphotransferases with an alcohol group as acceptor |
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#2: Chemical | ChemComp-SO4 / |
#3: Chemical | ChemComp-DQO / |
#4: 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: 2.95 Å3/Da / Density % sol: 58.29 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7 Details: Sodium citrate, Ammonium sulfate, hepes, 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: Jun 7, 2000 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→35 Å / Num. all: 20063 / Num. obs: 19421 / % possible obs: 96.8 % / Observed criterion σ(I): -3 / Redundancy: 6.5 % / Biso Wilson estimate: 41.2 Å2 / Rmerge(I) obs: 0.115 / Net I/σ(I): 8.4 |
Reflection shell | Resolution: 2.4→2.5 Å / Redundancy: 5.9 % / Rmerge(I) obs: 0.481 / Mean I/σ(I) obs: 1.2 / Num. unique all: 2621 / % possible all: 79.8 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 1WFC Resolution: 2.4→25 Å / Isotropic thermal model: anisotropic / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: mask / Bsol: 32.24 Å2 / ksol: 0.311 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 45.8 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.4→25 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.4→2.5 Å
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Refine LS restraints | *PLUS
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