3SFI
Ethionamide Boosters Part 2: Combining Bioisosteric Replacement and Structure-Based Drug Design to Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors.
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 6.7 | 293 | The crystallization buffer contained: 1.4 - 1.65M Ammonium Sulfate, 15% Glycerol and 0.1M MES pH6.7. , VAPOR DIFFUSION, HANGING DROP, temperature 293K |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.36 | 47.83 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 120.76 | α = 90 |
| b = 120.76 | β = 90 |
| c = 33.57 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 41 21 2 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | CCD | MARMOSAIC 300 mm CCD | 2010-12-06 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | SLS BEAMLINE X06DA | 1.0000 | SLS | X06DA |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (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 | 2.31 | 33.57 | 95.09 | 11439 | 10878 | 3 | |||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||||
| 1 | 2.31 | 2.37 | 99.7 | ||||||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | 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 | 1T56 | 2.31 | 32.34 | 10886 | 10878 | 547 | 99.93 | 0.22043 | 0.21775 | 0.2739 | RANDOM | 30.623 | |||||
| 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] | |
| 0.07 | 0.07 | -0.14 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 41.218 |
| r_dihedral_angle_4_deg | 19.72 |
| r_dihedral_angle_3_deg | 16.634 |
| r_dihedral_angle_1_deg | 5.952 |
| r_scangle_it | 4.595 |
| r_scbond_it | 2.897 |
| r_angle_refined_deg | 1.919 |
| r_mcangle_it | 1.736 |
| r_mcbond_it | 0.952 |
| r_chiral_restr | 0.116 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 1500 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 3 |
| Heterogen Atoms | 25 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| XDS | data scaling |
| MOLREP | phasing |
| REFMAC | refinement |
| XDS | data reduction |
| SCALA | data scaling |
