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Yorodumi- PDB-3k5u: Identification, SAR Studies and X-ray Cocrystal Analysis of a Nov... -
+Open data
-Basic information
Entry | Database: PDB / ID: 3k5u | ||||||
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Title | Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor | ||||||
Components | Serine/threonine-protein kinase 6 | ||||||
Keywords | TRANSFERASE / Aurora kinase inhibitors / Virtual screening / X-ray co-crystal analysis / Structure-based drug design (SBDD) / H-bonding / ATP-binding site / Cell cycle / Cytoskeleton / Kinase / Nucleotide-binding / Phosphoprotein / 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 / 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 / basolateral plasma membrane / peptidyl-serine phosphorylation / 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 / molecular replacement / Resolution: 2.35 Å | ||||||
Authors | Wu, J.S. / Leou, J.S. / Coumar, M.S. / Hsieh, H.P. / Wu, S.Y. | ||||||
Citation | Journal: Chemmedchem / Year: 2010 Title: Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor Authors: Coumar, M.S. / Tsai, M.T. / Chu, C.Y. / Uang, B.J. / Lin, W.H. / Chang, C.Y. / Chang, T.Y. / Leou, J.S. / Teng, C.H. / Wu, J.S. / Fang, M.Y. / Chen, C.H. / Hsu, J.T. / Wu, S.Y. / Chao, Y.S. / Hsieh, H.P. #1: 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. / 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 | 3k5u.cif.gz | 74.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb3k5u.ent.gz | 53.4 KB | Display | PDB format |
PDBx/mmJSON format | 3k5u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 3k5u_validation.pdf.gz | 735.3 KB | Display | wwPDB validaton report |
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Full document | 3k5u_full_validation.pdf.gz | 747.3 KB | Display | |
Data in XML | 3k5u_validation.xml.gz | 15.8 KB | Display | |
Data in CIF | 3k5u_validation.cif.gz | 22.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k5/3k5u ftp://data.pdbj.org/pub/pdb/validation_reports/k5/3k5u | HTTPS FTP |
-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: 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) / Gene: AURKA / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: O14965, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-PFQ / |
#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: 2.6 Å3/Da / Density % sol: 52.6 % / Mosaicity: 0.331 ° |
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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 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 29, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.35→30 Å / Num. obs: 14897 / % possible obs: 98.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.2 % / Rmerge(I) obs: 0.043 / Χ2: 1.059 / Net I/σ(I): 19.6 |
Reflection shell | Resolution: 2.35→2.43 Å / Redundancy: 6.3 % / Rmerge(I) obs: 0.444 / Num. unique all: 1435 / Χ2: 1.084 / % possible all: 99.8 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3FDN Resolution: 2.35→30 Å / Occupancy max: 1 / Occupancy min: 0.5 / Cross valid method: THROUGHOUT / Stereochemistry target values: Engh & Huber
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Displacement parameters | Biso max: 120.57 Å2 / Biso mean: 53.949 Å2 / Biso min: 23.72 Å2 | ||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.35→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.35→2.44 Å /
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