+Open data
-Basic information
Entry | Database: PDB / ID: 7o2v | ||||||
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Title | AURORA KINASE A IN COMPLEX WITH THE AUR-A/PDK1 INHIBITOR VI8 | ||||||
Components | Aurora kinase A | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE / KINASE / AURORA / INHIBITOR / CRYSTAL / COMPLEX / CANCER / TUMOR / DUAL / ATP-BINDING / STRUCTURE-BASED / DRUG DESIGN / SBDD | ||||||
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 / spindle pole centrosome / positive regulation of oocyte maturation / 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 / spindle pole centrosome / positive regulation of oocyte maturation / 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 / positive regulation of mitochondrial fission / spindle organization / 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 / AURKA Activation by TPX2 / mitotic spindle organization / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of mitotic nuclear division / ciliary basal body / negative regulation of protein binding / regulation of cytokinesis / regulation of signal transduction by p53 class mediator / 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 / mitotic spindle / spindle / kinetochore / response to wounding / microtubule cytoskeleton / G2/M transition of mitotic cell cycle / Regulation of PLK1 Activity at G2/M Transition / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / mitotic cell cycle / midbody / proteasome-mediated ubiquitin-dependent protein catabolic process / basolateral plasma membrane / peptidyl-serine phosphorylation / Regulation of TP53 Activity through Phosphorylation / microtubule / postsynaptic density / protein autophosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / protein heterodimerization activity / cell division / negative regulation of gene expression / protein phosphorylation / 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: 3.1 Å | ||||||
Authors | Garau, G. | ||||||
Citation | Journal: Eur.J.Med.Chem. / Year: 2021 Title: Development of potent dual PDK1/AurA kinase inhibitors for cancer therapy: Lead-optimization, structural insights, and ADME-Tox profile. Authors: Sestito, S. / Bacci, A. / Chiarugi, S. / Runfola, M. / Gado, F. / Margheritis, E. / Gul, S. / Riveiro, M.E. / Vazquez, R. / Huguet, S. / Manera, C. / Rezai, K. / Garau, G. / Rapposelli, S. #1: Journal: ACS Chem. Neurosci. / Year: 2016 Title: Dual Inhibition of PDK1 and Aurora Kinase A: An Effective Strategy to Induce Differentiation and Apoptosis of Human Glioblastoma Multiforme Stem Cells Authors: Simona Daniele, S. / Sestito, S. / Pietrobono, D. / Giacomelli, C. / Chiellini, G. / Di Maio, D. / Marinelli, L. / Novellino, E. / Martini, C. / Rapposelli, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7o2v.cif.gz | 154.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7o2v.ent.gz | 103.3 KB | Display | PDB format |
PDBx/mmJSON format | 7o2v.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o2/7o2v ftp://data.pdbj.org/pub/pdb/validation_reports/o2/7o2v | HTTPS FTP |
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-Related structure data
Related structure data | 3fdnS 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 34874.773 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: AURKA, AIK, AIRK1, ARK1, AURA, AYK1, BTAK, IAK1, STK15, STK6 Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: O14965, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-V0K / |
#3: Water | ChemComp-HOH / |
Has ligand of interest | N |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.32 Å3/Da / Density % sol: 47.01 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.2 M HEPES pH 7.5, 0.2 M (NH4)2SO4, 20% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ELETTRA / Beamline: 11.2C / Wavelength: 0.9785 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 18, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9785 Å / Relative weight: 1 |
Reflection | Resolution: 3.1→71.13 Å / Num. obs: 6602 / % possible obs: 100 % / Redundancy: 31 % / Biso Wilson estimate: 95.77 Å2 / CC1/2: 0.81 / Net I/σ(I): 4.7 |
Reflection shell | Resolution: 3.1→3.25 Å / Num. unique obs: 1149 / CC1/2: 0.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3FDN Resolution: 3.1→30.13 Å / SU ML: 0.5979 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 36.5043 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 112.53 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 3.1→30.13 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: -15.6484284122 Å / Origin y: -31.9693979447 Å / Origin z: 8.4320170281 Å
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Refinement TLS group | Selection details: all |