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Yorodumi- PDB-3fdn: Structure-based drug design of novel Aurora kinase A inhibitors: ... -
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-Basic information
Entry | Database: PDB / ID: 3fdn | ||||||
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Title | Structure-based drug design of novel Aurora kinase A inhibitors: Structure basis for potency and specificity | ||||||
Components | Serine/threonine-protein kinase 6Serine/threonine-specific protein kinase | ||||||
Keywords | TRANSFERASE / Aurora kinase inhibitors / Virtual screening / X-ray co-crystal analysis / Structure-based drug design (SBDD) / H-bonding. / ATP-binding / Cell cycle / Kinase / Nucleotide-binding / Phosphoprotein / Polymorphism / Serine/threonine-protein kinase | ||||||
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 / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of mitotic nuclear division / mitotic spindle organization / ciliary basal body / negative regulation of protein binding / regulation of signal transduction by p53 class mediator / regulation of cytokinesis / 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 / mitotic 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 / centrosome / protein serine/threonine kinase activity / 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: 1.9 Å | ||||||
Authors | Leou, J.S. / Wu, J.S. / Coumar, M.S. / Shukla, P. / Hsieh, H.P. / Wu, S.Y. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2009 Title: Structure-based drug design of novel Aurora kinase A inhibitors: structural basis for potency and specificity Authors: Coumar, M.S. / Leou, J.S. / Shukla, P. / Wu, J.S. / Dixit, A.K. / Lin, W.H. / Chang, C.Y. / Lien, T.W. / Tan, U.K. / Chen, C.H. / Hsu, J.T.A. / Chao, Y.S. / Wu, S.Y. / Hsieh, H.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 3fdn.cif.gz | 73.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3fdn.ent.gz | 53.6 KB | Display | PDB format |
PDBx/mmJSON format | 3fdn.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fd/3fdn ftp://data.pdbj.org/pub/pdb/validation_reports/fd/3fdn | HTTPS FTP |
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-Related structure data
Related structure data | 1mq4S 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: 32359.123 Da / Num. of mol.: 1 / Fragment: catalytic domain / Mutation: T288D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pET28a / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) References: UniProt: O14965, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-MMH / |
#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: 2.51 Å3/Da / Density % sol: 51.05 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.5 Details: 22% PEG400, 0.1mM ammonia sulfate, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: NSRRC / Beamline: BL13B1 |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 19, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Relative weight: 1 |
Reflection | Resolution: 1.9→30 Å / Num. obs: 27121 / % possible obs: 98 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.4 % / Rmerge(I) obs: 0.035 / Net I/σ(I): 28.94 |
Reflection shell | Resolution: 1.9→1.97 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.467 / Mean I/σ(I) obs: 2.56 / % possible all: 99.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB 1MQ4 Resolution: 1.9→30 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.909 / Cross valid method: THROUGHOUT / ESU R: 0.174 / ESU R Free: 0.172 / 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: 39.695 Å2
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Refinement step | Cycle: LAST / Resolution: 1.9→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.9→1.949 Å / Total num. of bins used: 20
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