3GHC
Design, Synthesis, and X-ray Crystal Structure of Classical and Nonclassical 2-amino-4-oxo-5-substituted-6-thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agenst
X-RAY DIFFRACTION
Starting Model(s)
Initial Refinement Model(s) | |||
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Type | Source | Accession Code | Details |
experimental model | PDB | 1U72 | PDB entry 1u72 |
Crystallization
Crystalization Experiments | ||||
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ID | Method | pH | Temperature | Details |
1 | VAPOR DIFFUSION, HANGING DROP | 6.9 | 298 | 100 mN KPO4, pH 6.9, 30% sat. AmSO4, 3% v/v ethanol, VAPOR DIFFUSION, HANGING DROP, temperature 298K |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.5 | 50.84 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 84.356 | α = 90 |
b = 84.356 | β = 90 |
c = 77.767 | γ = 120 |
Symmetry | |
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Space Group | H 3 |
Diffraction
Diffraction Experiment | ||||||||||||||
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ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
1 | 1 | x-ray | 200 | CCD | MARMOSAIC 325 mm CCD | mirrors | 2008-06-13 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
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ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | SSRL BEAMLINE BL11-1 | 0.9422 | SSRL | BL11-1 |
Data Collection
Overall | |||||||||||||||||||
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ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | R Sym I (Observed) | Net I Over Average Sigma (I) | Redundancy | Number Reflections (All) | Number Reflections (Observed) | Observed Criterion Sigma (F) | Observed Criterion Sigma (I) | B (Isotropic) From Wilson Plot | |||||||
1 | 1.3 | 53.22 | 99.8 | 0.045 | 0.022 | 5.3 | 50745 | 48164 | 2 | 2 | 14.6 |
Highest Resolution Shell | |||||||||||||||||||
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ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | R-Sym I (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||
1.3 | 1.37 | 99.3 | 0.143 | 0.075 | 10.3 | 4.3 | 7389 |
Refinement
Statistics | |||||||||||||||||||
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Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | Cut-off Sigma (I) | Cut-off Sigma (F) | Number Reflections (All) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (Observed) | R-Work | R-Free | R-Free Selection Details | Mean Isotropic B | |||
X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | PDB entry 1u72 | 1.3 | 22.51 | 2 | 1 | 50745 | 48155 | 2577 | 99.84 | 0.17143 | 0.17003 | 0.1985 | RANDOM | 14.473 |
Temperature Factor Modeling | ||||||
---|---|---|---|---|---|---|
Anisotropic B[1][1] | Anisotropic B[1][2] | Anisotropic B[1][3] | Anisotropic B[2][2] | Anisotropic B[2][3] | Anisotropic B[3][3] | |
0.01 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
r_dihedral_angle_2_deg | 34.77 |
r_dihedral_angle_4_deg | 15.204 |
r_dihedral_angle_3_deg | 13.483 |
r_dihedral_angle_1_deg | 6.372 |
r_scangle_it | 5.253 |
r_scbond_it | 3.432 |
r_angle_refined_deg | 2.58 |
r_mcangle_it | 2.291 |
r_mcbond_it | 1.346 |
r_chiral_restr | 0.551 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 1517 |
Nucleic Acid Atoms | |
Solvent Atoms | 341 |
Heterogen Atoms | 95 |
Software
Software | |
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Software Name | Purpose |
HKL-2000 | data collection |
MOLREP | phasing |
REFMAC | refinement |
MOSFLM | data reduction |
SCALA | data scaling |