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Yorodumi- PDB-5ei2: Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopola... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ei2 | ||||||
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Title | Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle kinase 1 (MPS1) Using a Structure-Based Hydridization Approach | ||||||
Components | Dual specificity protein kinase TTK | ||||||
Keywords | TRANSFERASE / Spindle Assembly Checkpoint (SAC) / Oncology target Pyrido[3 / 4-d]pyrimidine based inhibitors Selective against MPS1 | ||||||
Function / homology | Function and homology information protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / protein serine/threonine/tyrosine kinase activity / mitotic spindle organization ...protein localization to meiotic spindle midzone / meiotic spindle assembly checkpoint signaling / kinetochore binding / female meiosis chromosome segregation / protein localization to kinetochore / dual-specificity kinase / spindle organization / mitotic spindle assembly checkpoint signaling / protein serine/threonine/tyrosine kinase activity / mitotic spindle organization / chromosome segregation / spindle / kinetochore / protein tyrosine kinase activity / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of cell population proliferation / ATP binding / membrane / identical protein binding / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / Resolution: 2.67 Å | ||||||
Authors | Innocenti, P. / Woodward, H.L. / Solanki, S. / Naud, N. / Westwood, I.M. / Cronin, N. / Hayes, A. / Roberts, J. / Henley, A.T. / Baker, R. ...Innocenti, P. / Woodward, H.L. / Solanki, S. / Naud, N. / Westwood, I.M. / Cronin, N. / Hayes, A. / Roberts, J. / Henley, A.T. / Baker, R. / Faisal, A. / Mak, G. / Box, G. / Valenti, M. / De Haven Brandon, A. / O'Fee, L. / Saville, J. / Schmitt, J. / Burke, R. / van Montfort, R.L.M. / Raymaud, F.I. / Eccles, S.A. / Linardopoulos, S. / Blagg, J. / Hoelder, S. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: J.Med.Chem. / Year: 2016 Title: Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. Authors: Innocenti, P. / Woodward, H.L. / Solanki, S. / Naud, S. / Westwood, I.M. / Cronin, N. / Hayes, A. / Roberts, J. / Henley, A.T. / Baker, R. / Faisal, A. / Mak, G.W. / Box, G. / Valenti, M. / ...Authors: Innocenti, P. / Woodward, H.L. / Solanki, S. / Naud, S. / Westwood, I.M. / Cronin, N. / Hayes, A. / Roberts, J. / Henley, A.T. / Baker, R. / Faisal, A. / Mak, G.W. / Box, G. / Valenti, M. / De Haven Brandon, A. / O'Fee, L. / Saville, H. / Schmitt, J. / Matijssen, B. / Burke, R. / van Montfort, R.L. / Raynaud, F.I. / Eccles, S.A. / Linardopoulos, S. / Blagg, J. / Hoelder, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ei2.cif.gz | 113.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ei2.ent.gz | 92.1 KB | Display | PDB format |
PDBx/mmJSON format | 5ei2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ei/5ei2 ftp://data.pdbj.org/pub/pdb/validation_reports/ei/5ei2 | HTTPS FTP |
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-Related 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: 36115.258 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: N-(2,4-dimethoxyphenyl)-8-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-d]pyrimidin-2-amine Source: (gene. exp.) Homo sapiens (human) / Gene: TTK, MPS1, MPS1L1 / Production host: Escherichia coli (E. coli) / References: UniProt: P33981, dual-specificity kinase |
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#2: Chemical | ChemComp-5O7 / ~{ |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 2.73 Å3/Da / Density % sol: 55 % |
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Crystal grow | Temperature: 291.15 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 0.1 M Bis-Tris propane 0.2 M MgCl2 0.2 M Sodium formate 20% PEG3350 PH range: 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-X / Wavelength: 1.54 Å |
Detector | Type: DECTRIS PILATUS 300K / Detector: PIXEL / Date: Apr 9, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.66→39.76 Å / Num. obs: 11505 / % possible obs: 99.4 % / Redundancy: 16.2 % / Biso Wilson estimate: 102.57 Å2 / Net I/σ(I): 9.4 |
-Processing
Software |
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Refinement | Resolution: 2.67→20.31 Å / Cor.coef. Fo:Fc: 0.9436 / Cor.coef. Fo:Fc free: 0.9249 / SU R Cruickshank DPI: 0.538 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.529 / SU Rfree Blow DPI: 0.338 / SU Rfree Cruickshank DPI: 0.344
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Displacement parameters | Biso mean: 96.02 Å2
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Refine analyze | Luzzati coordinate error obs: 0.501 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.67→20.31 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.67→2.98 Å / Total num. of bins used: 5
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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