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Yorodumi- PDB-3rtp: Design and synthesis of brain penetrant selective JNK inhibitors ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3rtp | ||||||
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Title | Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration | ||||||
Components | Mitogen-activated protein kinase 10 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / JNK inhibitors / pharmacokinetic properties / neurodegeneration / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information JUN kinase activity / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / MAP kinase kinase activity / response to light stimulus / mitogen-activated protein kinase / JNK cascade / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / FCERI mediated MAPK activation / regulation of circadian rhythm ...JUN kinase activity / Activation of the AP-1 family of transcription factors / Fc-epsilon receptor signaling pathway / MAP kinase kinase activity / response to light stimulus / mitogen-activated protein kinase / JNK cascade / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / FCERI mediated MAPK activation / regulation of circadian rhythm / cellular senescence / rhythmic process / Oxidative Stress Induced Senescence / protein phosphorylation / protein serine kinase activity / signal transduction / mitochondrion / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Bowers, S. / Truong, A.P. / Neitz, R.J. / Hom, R.K. / Sealy, J.M. / Probst, G.D. / Quincy, Q. / Peterson, B. / Chan, W. / Galemmo Jr., R.A. ...Bowers, S. / Truong, A.P. / Neitz, R.J. / Hom, R.K. / Sealy, J.M. / Probst, G.D. / Quincy, Q. / Peterson, B. / Chan, W. / Galemmo Jr., R.A. / Konradi, A.W. / Sham, H.L. / Pan, H. / Lin, M. / Yao, N. / Artis, D.R. / Zhang, H. / Chen, L. / Dryer, M. / Samant, B. / Zmolek, W. / Wong, K. / Lorentzen, C. / Goldbach, E. / Tonn, G. / Quinn, K.P. / Sauer, J. / Wright, S. / Powell, K. / Ruslim, L. / Ren, Z. / Bard, F. / Yednock, T.A. / Griswold-Prenne, I. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2011 Title: Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration. Authors: Bowers, S. / Truong, A.P. / Jeffrey Neitz, R. / Hom, R.K. / Sealy, J.M. / Probst, G.D. / Quincy, D. / Peterson, B. / Chan, W. / Galemmo, R.A. / Konradi, A.W. / Sham, H.L. / Toth, G. / Pan, H. ...Authors: Bowers, S. / Truong, A.P. / Jeffrey Neitz, R. / Hom, R.K. / Sealy, J.M. / Probst, G.D. / Quincy, D. / Peterson, B. / Chan, W. / Galemmo, R.A. / Konradi, A.W. / Sham, H.L. / Toth, G. / Pan, H. / Lin, M. / Yao, N. / Artis, D.R. / Zhang, H. / Chen, L. / Dryer, M. / Samant, B. / Zmolek, W. / Wong, K. / Lorentzen, C. / Goldbach, E. / Tonn, G. / Quinn, K.P. / Sauer, J.M. / Wright, S. / Powell, K. / Ruslim, L. / Ren, Z. / Bard, F. / Yednock, T.A. / Griswold-Prenner, I. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3rtp.cif.gz | 73.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3rtp.ent.gz | 52.5 KB | Display | PDB format |
PDBx/mmJSON format | 3rtp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rt/3rtp ftp://data.pdbj.org/pub/pdb/validation_reports/rt/3rtp | HTTPS FTP |
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-Related structure data
Similar structure data |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 41870.438 Da / Num. of mol.: 1 / Fragment: UNP residues 40-401 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK10, JNK3, JNK3A, PRKM10 / Production host: Escherichia coli (E. coli) References: UniProt: P53779, mitogen-activated protein kinase |
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#2: Chemical | ChemComp-34I / |
#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: 2.33 Å3/Da / Density % sol: 47.26 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 15% PEG 8K, 10% ethylene glycol, 0.1M Hepes pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 180 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å |
Detector | Type: RIGAKU RAXIS HTC / Detector: IMAGE PLATE / Date: Jun 13, 2008 |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→59.79 Å / Num. obs: 10425 / % possible obs: 96.8 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 |
Reflection shell | Resolution: 2.4→2.49 Å / % possible all: 95.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→38.49 Å / Cor.coef. Fo:Fc: 0.872 / Cor.coef. Fo:Fc free: 0.734 / SU B: 45.842 / SU ML: 0.72 / Cross valid method: THROUGHOUT / ESU R Free: 0.909 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: 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 / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24.095 Å2
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Refinement step | Cycle: LAST / Resolution: 2.4→38.49 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.301→2.391 Å / Total num. of bins used: 20
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