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- PDB-1juj: Human Thymidylate Synthase Bound to dUMP and LY231514, a Pyrrolo(... -
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Open data
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Basic information
Entry | Database: PDB / ID: 1juj | ||||||
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Title | Human Thymidylate Synthase Bound to dUMP and LY231514, a Pyrrolo(2,3-d)pyrimidine-based Antifolate | ||||||
![]() | THYMIDYLATE SYNTHASE | ||||||
![]() | TRANSFERASE / cancer / dTMP synthesis / antifolate / drug resistance | ||||||
Function / homology | ![]() uracil metabolic process / response to organophosphorus / intestinal epithelial cell maturation / response to folic acid / Interconversion of nucleotide di- and triphosphates / thymidylate synthase / response to vitamin A / 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 / thymidylate synthase / response to vitamin A / 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 / response to glucocorticoid / mRNA regulatory element binding translation repressor activity / response to cytokine / response to progesterone / 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 | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Sayre, P.H. / Finer-Moore, J.S. / Fritz, T.A. / Biermann, D. / Gates, S.B. / MacKellar, W.C. / Patel, V.F. / Stroud, R.M. | ||||||
![]() | ![]() Title: Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases. Authors: Sayre, P.H. / Finer-Moore, J.S. / Fritz, T.A. / Biermann, D. / Gates, S.B. / MacKellar, W.C. / Patel, V.F. / Stroud, R.M. #1: ![]() Title: Crystal Structure of Human Thymidylate Synthase: A Structural Mechanism for Guiding Substrates into the Active Site Authors: Schiffer, C.A. / Clifton, I.J. / Davisson, V.J. / Santi, D.V. / Stroud, R.M. | ||||||
History |
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Remark 295 | NON-CRYSTALLOGRAPHIC SYMMETRY THE TRANSFORMATIONS PRESENTED ON THE MTRIX RECORDS BELOW DESCRIBE NON- ...NON-CRYSTALLOGRAPHIC SYMMETRY THE TRANSFORMATIONS PRESENTED ON THE MTRIX RECORDS BELOW DESCRIBE NON-CRYSTALLOGRAPHIC RELATIONSHIPS AMONG ATOMS IN THIS ENTRY. APPLYING THE APPROPRIATE MTRIX TRANSFORMATION TO THE RESIDUES LISTED FIRST WILL YIELD APPROXIMATE COORDINATES FOR THE RESIDUES LISTED SECOND. CHAIN IDENTIFIERS GIVEN AS "?" REFER TO CHAINS FOR WHICH ATOMS ARE NOT FOUND IN THIS ENTRY. APPLIED TO TRANSFORMED TO TRANSFORM CHAIN RESIDUES CHAIN RESIDUES RMSD SSS M 1 A 28 .. 313 B 28 .. 313 M 2 A 28 .. 313 C 28 .. 313 M 3 A 28 .. 313 D 28 .. 313 WHERE SSS -> COLUMNS 8-10 OF MTRIX RECORDS REMARK: THE AUTHORS RESTRAINED SUBUNIT B, C, AND D AGAINST SUBUNIT A, USING A WEIGHT OF 200 KCAL/MOL-A, AND SIGB OF 2 A2. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 233.4 KB | Display | ![]() |
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PDB format | ![]() | 190.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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2 | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS oper:
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Details | The biological dimer is generated from the coordinates with the following noncrystallographic symmetry rotation matrix and translation vector: {* real-space rotation matrix *} {===>} ncs_matrix_2=( -0.04364 0.52546 -0.84970 ) ( 0.53532 -0.70580 -0.46397 ) ( -0.84352 -0.47511 -0.25049 ); {* real-space translation vector *} {===>} ncs_vector_2=(-22.64756 -91.22199 -82.72397); A second dimer in the asymmetric unit is generated by the following NCS symmetry operations: {* real-space rotation matrix *} {===>} ncs_matrix_3=( -0.99996 0.00926 -0.00060 ) ( 0.00927 0.99993 -0.00771 ) ( 0.00053 -0.00771 -0.99997 ); {* real-space translation vector *} {===>} ncs_vector_3=(-48.72274 4.78975 -52.76192); and {* real-space rotation matrix *} {===>} ncs_matrix_4=( 0.04749 -0.53294 0.84482 ) ( 0.54116 -0.69717 -0.47021 ) ( 0.83958 0.47951 0.25530 ); {* real-space translation vector *} {===>} ncs_vector_4=(-27.02831 -85.96681 30.66597); |
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Components
#1: Protein | Mass: 35734.859 Da / Num. of mol.: 4 / Mutation: R46E Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-UMP / #3: Chemical | ChemComp-LYA / |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.48 Å3/Da / Density % sol: 50.47 % | ||||||||||||||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 296 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: PEG-monomethyl ether 5000, sodium cacodylate, ammonium sulfate, KCL, TRIS, EDTA, DTT, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 296K | ||||||||||||||||||||||||||||||||||||||||||
Crystal grow | *PLUS | ||||||||||||||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 296 K |
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Diffraction source | Source: ![]() |
Detector | Type: RIGAKU RAXIS II / Detector: IMAGE PLATE / Date: Jul 1, 1997 |
Radiation | Monochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54178 Å / Relative weight: 1 |
Reflection | Resolution: 3→40 Å / Num. all: 23396 / Num. obs: 23396 / % possible obs: 84 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 2.1 % / Rmerge(I) obs: 0.145 / Net I/σ(I): 5.8 |
Reflection shell | Resolution: 3→3.09 Å / Rmerge(I) obs: 0.43 / Mean I/σ(I) obs: 1.8 / % possible all: 78 |
Reflection | *PLUS Highest resolution: 3 Å / Lowest resolution: 40 Å / % possible obs: 84 % / Num. measured all: 50715 |
Reflection shell | *PLUS % possible obs: 78 % |
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Processing
Software |
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Refinement | Method to determine structure: ![]() Starting model: thymidylate synthase from Leishmania major Resolution: 3→37.96 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 131081.01 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh and Huber Details: The asymmetric unit contains four monomers and these were refined using strict noncrystallographic symmetry constraints. The strict noncrystallographic symmetry was broken at the interface ...Details: The asymmetric unit contains four monomers and these were refined using strict noncrystallographic symmetry constraints. The strict noncrystallographic symmetry was broken at the interface between the two dimers and Arg42 at this interface in chains B and D had to be rebuilt at the end of refinement. Residues 1-27, as well as the sidechain of Arg147 are disordered in each monomer and are omitted from the structure.
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 30.2028 Å2 / ksol: 0.273945 e/Å3 | |||||||||||||||||||||||||
Displacement parameters | Biso mean: 25.2 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 3→37.96 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3→3.19 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 6
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Xplor file |
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Software | *PLUS Name: CNS / Version: 1 / Classification: refinement | |||||||||||||||||||||||||
Refinement | *PLUS σ(F): 0 / % reflection Rfree: 9.9 % / Rfactor all: 0.273 / Rfactor obs: 0.268 | |||||||||||||||||||||||||
Solvent computation | *PLUS | |||||||||||||||||||||||||
Displacement parameters | *PLUS Biso mean: 25.2 Å2 | |||||||||||||||||||||||||
Refine LS restraints | *PLUS
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LS refinement shell | *PLUS Rfactor Rfree: 0.482 / % reflection Rfree: 10.1 % / Rfactor Rwork: 0.431 |