+Open data
-Basic information
Entry | Database: PDB / ID: 4o1u | ||||||
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Title | Crystal structure of human thymidylate synthase mutant Y202C | ||||||
Components | Thymidylate synthase | ||||||
Keywords | TRANSFERASE / Dimer-dimer interface modification / inactive conformation / Methyltransferase / Nucleotide biosynthesis | ||||||
Function / homology | Function and homology information uracil metabolic process / response to organophosphorus / intestinal epithelial cell maturation / response to folic acid / Interconversion of nucleotide di- and triphosphates / response to vitamin A / thymidylate synthase / sequence-specific mRNA binding / cartilage development / tetrahydrofolate interconversion ...uracil metabolic process / response to organophosphorus / intestinal epithelial cell maturation / response to folic acid / Interconversion of nucleotide di- and triphosphates / response to vitamin A / thymidylate synthase / sequence-specific mRNA binding / cartilage development / tetrahydrofolate interconversion / thymidylate synthase activity / folic acid binding / dTMP biosynthetic process / dTTP biosynthetic process / DNA biosynthetic process / G1/S-Specific Transcription / developmental growth / dihydrofolate reductase activity / response to glucocorticoid / mRNA regulatory element binding translation repressor activity / response to progesterone / response to cytokine / liver regeneration / response to toxic substance / circadian rhythm / methylation / response to ethanol / mitochondrial inner membrane / negative regulation of translation / mitochondrial matrix / response to xenobiotic stimulus / protein homodimerization activity / mitochondrion / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.26 Å | ||||||
Authors | Pozzi, C. / Mangani, S. | ||||||
Citation | Journal: Elife / Year: 2022 Title: Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth. Authors: Costantino, L. / Ferrari, S. / Santucci, M. / Salo-Ahen, O.M.H. / Carosati, E. / Franchini, S. / Lauriola, A. / Pozzi, C. / Trande, M. / Gozzi, G. / Saxena, P. / Cannazza, G. / Losi, L. / ...Authors: Costantino, L. / Ferrari, S. / Santucci, M. / Salo-Ahen, O.M.H. / Carosati, E. / Franchini, S. / Lauriola, A. / Pozzi, C. / Trande, M. / Gozzi, G. / Saxena, P. / Cannazza, G. / Losi, L. / Cardinale, D. / Venturelli, A. / Quotadamo, A. / Linciano, P. / Tagliazucchi, L. / Moschella, M.G. / Guerrini, R. / Pacifico, S. / Luciani, R. / Genovese, F. / Henrich, S. / Alboni, S. / Santarem, N. / da Silva Cordeiro, A. / Giovannetti, E. / Peters, G.J. / Pinton, P. / Rimessi, A. / Cruciani, G. / Stroud, R.M. / Wade, R.C. / Mangani, S. / Marverti, G. / D'Arca, D. / Ponterini, G. / Costi, M.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4o1u.cif.gz | 231.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4o1u.ent.gz | 186 KB | Display | PDB format |
PDBx/mmJSON format | 4o1u.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/o1/4o1u ftp://data.pdbj.org/pub/pdb/validation_reports/o1/4o1u | HTTPS FTP |
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-Related structure data
Related structure data | 4o1xC 3n5gS C: citing same article (ref.) 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
#1: Protein | Mass: 37398.934 Da / Num. of mol.: 2 / Mutation: Y202C Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OK/SW-cl.29, TS, TYMS, TYSM / Plasmid: pQE-80L / Production host: Escherichia coli (E. coli) / References: UniProt: P04818, thymidylate synthase #2: Chemical | ChemComp-SO4 / #3: Chemical | ChemComp-EDO / #4: Chemical | #5: Water | ChemComp-HOH / | |
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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: 2.99 Å3/Da / Density % sol: 58.92 % |
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Crystal grow | Temperature: 300 K / Method: vapor diffusion, hanging drop / pH: 8.3 Details: 35% saturated Ammonium Sulfate + 20mM BME + 0.1M TRIS, pH 8.3, VAPOR DIFFUSION, HANGING DROP, temperature 300K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.936 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Dec 5, 2009 |
Radiation | Monochromator: Si(311), Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.936 Å / Relative weight: 1 |
Reflection | Resolution: 2.26→48.12 Å / Num. all: 43550 / Num. obs: 39688 / % possible obs: 97.6 % / Observed criterion σ(I): 2 / Redundancy: 3.8 % / Biso Wilson estimate: 47.3 Å2 / Rmerge(I) obs: 0.067 / Net I/σ(I): 12 |
Reflection shell | Resolution: 2.26→2.38 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.378 / Mean I/σ(I) obs: 3.7 / Num. unique all: 5882 / % possible all: 98.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: pdb entry 3N5G Resolution: 2.26→48.12 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.948 / SU B: 8.715 / SU ML: 0.106 / Cross valid method: THROUGHOUT / ESU R: 0.189 / ESU R Free: 0.168 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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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: 54.166 Å2
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Refinement step | Cycle: LAST / Resolution: 2.26→48.12 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.26→2.319 Å / Total num. of bins used: 20
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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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