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Yorodumi- PDB-4li8: TANKYRASE-1 complexed with small molecule inhibitor 2-[4-(4-fluor... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4li8 | ||||||
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Title | TANKYRASE-1 complexed with small molecule inhibitor 2-[4-(4-fluorobenzoyl)piperidin-1-yl]-N-[(4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-yl)methyl]-N-(thiophen-2-ylmethyl)acetamide | ||||||
Components | Tankyrase-1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | Function and homology information negative regulation of telomeric DNA binding / negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric / regulation of telomere maintenance via telomerase / XAV939 stabilizes AXIN / NAD+ ADP-ribosyltransferase / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / protein poly-ADP-ribosylation / pericentriolar material ...negative regulation of telomeric DNA binding / negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric / regulation of telomere maintenance via telomerase / XAV939 stabilizes AXIN / NAD+ ADP-ribosyltransferase / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / protein poly-ADP-ribosylation / pericentriolar material / mitotic spindle pole / NAD+-protein ADP-ribosyltransferase activity / positive regulation of telomere capping / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ ADP-ribosyltransferase activity / spindle assembly / mRNA transport / nuclear pore / positive regulation of telomerase activity / positive regulation of telomere maintenance via telomerase / nucleotidyltransferase activity / mitotic spindle organization / TCF dependent signaling in response to WNT / Degradation of AXIN / peptidyl-threonine phosphorylation / Wnt signaling pathway / Regulation of PTEN stability and activity / protein polyubiquitination / positive regulation of canonical Wnt signaling pathway / protein transport / histone binding / peptidyl-serine phosphorylation / nuclear membrane / chromosome, telomeric region / nuclear body / Ub-specific processing proteases / cell division / Golgi membrane / Golgi apparatus / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER METHODS / Resolution: 2.521 Å | ||||||
Authors | Kirby, C.A. / Stams, T. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Identification of NVP-TNKS656: The Use of Structure-Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor. Authors: Shultz, M.D. / Cheung, A.K. / Kirby, C.A. / Firestone, B. / Fan, J. / Chen, C.H. / Chen, Z. / Chin, D.N. / Dipietro, L. / Fazal, A. / Feng, Y. / Fortin, P.D. / Gould, T. / Lagu, B. / Lei, H. ...Authors: Shultz, M.D. / Cheung, A.K. / Kirby, C.A. / Firestone, B. / Fan, J. / Chen, C.H. / Chen, Z. / Chin, D.N. / Dipietro, L. / Fazal, A. / Feng, Y. / Fortin, P.D. / Gould, T. / Lagu, B. / Lei, H. / Lenoir, F. / Majumdar, D. / Ochala, E. / Palermo, M.G. / Pham, L. / Pu, M. / Smith, T. / Stams, T. / Tomlinson, R.C. / Toure, B.B. / Visser, M. / Wang, R.M. / Waters, N.J. / Shao, W. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4li8.cif.gz | 98.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4li8.ent.gz | 75.3 KB | Display | PDB format |
PDBx/mmJSON format | 4li8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/li/4li8 ftp://data.pdbj.org/pub/pdb/validation_reports/li/4li8 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 25409.711 Da / Num. of mol.: 2 / Fragment: CATALYTIC DOMAIN, UNP residues 1105-1325 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 / Production host: Escherichia coli (E. coli) / References: UniProt: O95271, NAD+ ADP-ribosyltransferase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / #5: Water | ChemComp-HOH / | Sequence details | SEQUENCE CONFLICT M1266I PRESENT IN UNP ENTRY O95271 | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.33 Å3/Da / Density % sol: 47.18 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.8 Details: EQUAL VOLUMES (2 UL) OF RESERVIOR SOLUTION AND PROTEIN SOLUTION WERE MIXED AND SET AS HANGING DROPS. 15% PEG3350, 100MM BIS-TRIS PH5.8, 310MM AMMONIUM SULFATE. PROTEIN SOLUTION: 20 MG/ML IN ...Details: EQUAL VOLUMES (2 UL) OF RESERVIOR SOLUTION AND PROTEIN SOLUTION WERE MIXED AND SET AS HANGING DROPS. 15% PEG3350, 100MM BIS-TRIS PH5.8, 310MM AMMONIUM SULFATE. PROTEIN SOLUTION: 20 MG/ML IN 25 MM TRIS PH8, 200MM NACL, 1MM TCEP, 1MM PJ34. CRYSTALS WERE THEN MOVED INTO A SOAKING SOLUTION CONTAINING 18% PEG 3350, 320MM AMMONIUM SULFATE, 100MM BIS- TRIS PH 5.8, 0.2 MM inhibitor. , VAPOR DIFFUSION, HANGING DROP, temperature 298K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 / Wavelength: 1 Å | |||||||||
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Feb 1, 2009 | |||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||
Radiation wavelength |
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Reflection | Resolution: 2.521→50 Å / Num. obs: 15321 / % possible obs: 98.2 % / Redundancy: 3.17 % / Rmerge(I) obs: 0.105 / Net I/σ(I): 9.41 | |||||||||
Reflection shell | Resolution: 2.521→2.67 Å / Redundancy: 3.25 % / Rmerge(I) obs: 0.353 / Mean I/σ(I) obs: 3.57 / % possible all: 98.7 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER METHODS / Resolution: 2.521→44.039 Å / σ(F): 1.36
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Displacement parameters | Biso mean: 35.17 Å2
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Refine analyze | Luzzati coordinate error obs: 0.37 Å | ||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.521→44.039 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.521→2.7156 Å
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