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Yorodumi- PDB-3r22: Design, synthesis, and biological evaluation of pyrazolopyridine-... -
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-Basic information
Entry | Database: PDB / ID: 3r22 | ||||||
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Title | Design, synthesis, and biological evaluation of pyrazolopyridine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I) | ||||||
Components | Serine/threonine-protein kinase 6 | ||||||
Keywords | transferase/transferase inhibitor / Kinase domain / transferase-transferase inhibitor complex | ||||||
Function / homology | Function and homology information Interaction between PHLDA1 and AURKA / regulation of centrosome cycle / axon hillock / spindle assembly involved in female meiosis I / cilium disassembly / positive regulation of oocyte maturation / spindle pole centrosome / histone H3S10 kinase activity / chromosome passenger complex / pronucleus ...Interaction between PHLDA1 and AURKA / regulation of centrosome cycle / axon hillock / spindle assembly involved in female meiosis I / cilium disassembly / positive regulation of oocyte maturation / spindle pole centrosome / histone H3S10 kinase activity / chromosome passenger complex / pronucleus / meiotic spindle / mitotic centrosome separation / germinal vesicle / protein localization to centrosome / anterior/posterior axis specification / centrosome localization / neuron projection extension / spindle organization / positive regulation of mitochondrial fission / mitotic spindle pole / SUMOylation of DNA replication proteins / spindle midzone / regulation of G2/M transition of mitotic cell cycle / centriole / protein serine/threonine/tyrosine kinase activity / positive regulation of mitotic cell cycle / positive regulation of mitotic nuclear division / AURKA Activation by TPX2 / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / mitotic spindle organization / ciliary basal body / regulation of cytokinesis / regulation of signal transduction by p53 class mediator / negative regulation of protein binding / molecular function activator activity / liver regeneration / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / regulation of protein stability / spindle microtubule / mitotic spindle / kinetochore / response to wounding / spindle / G2/M transition of mitotic cell cycle / microtubule cytoskeleton / Regulation of PLK1 Activity at G2/M Transition / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / mitotic cell cycle / midbody / peptidyl-serine phosphorylation / basolateral plasma membrane / proteasome-mediated ubiquitin-dependent protein catabolic process / Regulation of TP53 Activity through Phosphorylation / protein autophosphorylation / postsynaptic density / non-specific serine/threonine protein kinase / protein kinase activity / protein heterodimerization activity / cell division / protein phosphorylation / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / glutamatergic synapse / apoptotic process / ubiquitin protein ligase binding / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / nucleoplasm / ATP binding / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å | ||||||
Authors | Zhang, L. / Fan, J. / Chong, J.-H. / Cesana, A. / Tam, B. / Gilson, C. / Boykin, C. / Wang, D. / Marcotte, D. / Le Brazidec, J.-Y. ...Zhang, L. / Fan, J. / Chong, J.-H. / Cesana, A. / Tam, B. / Gilson, C. / Boykin, C. / Wang, D. / Marcotte, D. / Le Brazidec, J.-Y. / Aivazian, D. / Piao, J. / Lundgren, K. / Hong, K. / Vu, K. / Nguyen, K. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2011 Title: Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I). Authors: Zhang, L. / Fan, J. / Chong, J.H. / Cesena, A. / Tam, B.Y. / Gilson, C. / Boykin, C. / Wang, D. / Aivazian, D. / Marcotte, D. / Xiao, G. / Le Brazidec, J.Y. / Piao, J. / Lundgren, K. / Hong, ...Authors: Zhang, L. / Fan, J. / Chong, J.H. / Cesena, A. / Tam, B.Y. / Gilson, C. / Boykin, C. / Wang, D. / Aivazian, D. / Marcotte, D. / Xiao, G. / Le Brazidec, J.Y. / Piao, J. / Lundgren, K. / Hong, K. / Vu, K. / Nguyen, K. / Gan, L.S. / Silvian, L. / Ling, L. / Teng, M. / Reff, M. / Takeda, N. / Timple, N. / Wang, Q. / Morena, R. / Khan, S. / Zhao, S. / Li, T. / Lee, W.C. / Taveras, A.G. / Chao, J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3r22.cif.gz | 66.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3r22.ent.gz | 48.1 KB | Display | PDB format |
PDBx/mmJSON format | 3r22.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3r22_validation.pdf.gz | 734.5 KB | Display | wwPDB validaton report |
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Full document | 3r22_full_validation.pdf.gz | 744.4 KB | Display | |
Data in XML | 3r22_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | 3r22_validation.cif.gz | 16.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r2/3r22 ftp://data.pdbj.org/pub/pdb/validation_reports/r2/3r22 | HTTPS FTP |
-Related structure data
Related structure data | 3r21C 3fdnS C: citing same article (ref.) 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: 31346.939 Da / Num. of mol.: 1 / Fragment: unp residues 126-391 / Mutation: T287D, T288D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AURKA, AIK, ARK1, AURA, BTAK, STK15, STK6 / Plasmid: pDEST20 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O14965, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-D37 / |
#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: 2.54 Å3/Da / Density % sol: 51.52 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 9 Details: 10% Peg550 MME, 0.1M Tris pH 9, 10% ethylene glycol, VAPOR DIFFUSION, SITTING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 193 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.9793 Å |
Detector | Type: RAYONIX MX-225 / Detector: CCD / Date: Jun 11, 2008 / Details: Diamond (111)monochromator |
Radiation | Monochromator: Diamond (111) Monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 |
Reflection | Resolution: 2.9→50 Å / Num. obs: 7345 / % possible obs: 99.8 % / Observed criterion σ(I): 2 / Redundancy: 9.8 % / Biso Wilson estimate: 106 Å2 / Rmerge(I) obs: 0.051 / Net I/σ(I): 50.15 |
Reflection shell | Resolution: 2.9→3 Å / Redundancy: 10.6 % / Rmerge(I) obs: 0.567 / Mean I/σ(I) obs: 4.1 / Num. unique all: 746 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 3FDN Resolution: 2.9→40.7 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.893 / SU B: 21.536 / SU ML: 0.366 / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / ESU R Free: 0.104 / 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: 1.4 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 77.931 Å2
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Refine analyze | Luzzati coordinate error obs: 0.514 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.9→40.7 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.898→2.973 Å / Total num. of bins used: 20
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