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Yorodumi- PDB-6sfk: Crystal structure of p38 alpha in complex with compound 81 (MCP42) -
+Open data
-Basic information
Entry | Database: PDB / ID: 6sfk | ||||||
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Title | Crystal structure of p38 alpha in complex with compound 81 (MCP42) | ||||||
Components | Mitogen-activated protein kinase 14MAPK14 | ||||||
Keywords | TRANSFERASE / p38a / MAPK / MAPK14 / kinase inhibitor / Structural Genomics / Structural Genomics Consortium / SGC | ||||||
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 / MOLECULAR REPLACEMENT / Resolution: 1.8 Å | ||||||
Authors | Chaikuad, A. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Fast Iterative Synthetic Approach toward Identification of Novel Highly Selective p38 MAP Kinase Inhibitors. Authors: Rohm, S. / Berger, B.T. / Schroder, M. / Chaikuad, A. / Winkel, R. / Hekking, K.F.W. / Benningshof, J.J.C. / Muller, G. / Tesch, R. / Kudolo, M. / Forster, M. / Laufer, S. / Knapp, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6sfk.cif.gz | 156.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6sfk.ent.gz | 122.4 KB | Display | PDB format |
PDBx/mmJSON format | 6sfk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sf/6sfk ftp://data.pdbj.org/pub/pdb/validation_reports/sf/6sfk | HTTPS FTP |
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-Related structure data
Related structure data | 6sfiC 6sfjC 5larS 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: 41395.211 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A / Plasmid: pET-Duet1 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): -R3-pRARE2 References: UniProt: Q16539, mitogen-activated protein kinase | ||||||
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#2: Chemical | ChemComp-EDO / #3: Chemical | ChemComp-LB8 / ~{ | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.38 Å3/Da / Density % sol: 48.22 % |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 17.5% MMW PEG smears, 0.1M MES pH 6.0 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92819 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Feb 26, 2016 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.92819 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 1.8→50.4 Å / Num. obs: 37064 / % possible obs: 99.6 % / Redundancy: 6.7 % / CC1/2: 0.999 / Rmerge(I) obs: 0.059 / Rpim(I) all: 0.026 / Rrim(I) all: 0.063 / Net I/σ(I): 14.2 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5LAR Resolution: 1.8→50.4 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.948 / SU B: 5.4 / SU ML: 0.086 / SU R Cruickshank DPI: 0.1194 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.119 / ESU R Free: 0.117 Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 93.43 Å2 / Biso mean: 37.609 Å2 / Biso min: 17.36 Å2
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Refinement step | Cycle: final / Resolution: 1.8→50.4 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.8→1.847 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 6.74 Å / Origin y: 42.109 Å / Origin z: 16.04 Å
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