3FLI
Discovery of XL335, a Highly Potent, Selective and Orally-Active Agonist of the Farnesoid X Receptor (FXR)
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 8.5 | 292 | 22% PEG4K, 150 mM sodium acetate, 75 mM Tris, pH 8.5, VAPOR DIFFUSION, HANGING DROP, temperature 292K |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.57 | 52.22 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 66.519 | α = 90 |
| b = 66.519 | β = 90 |
| c = 125.434 | 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 | ADSC QUANTUM 210 | 2004-11-18 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | ALS BEAMLINE 5.0.1 | 1.00000 | ALS | 5.0.1 |
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 | 66.519 | 96.9 | 19746 | |||||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||||
| 2 | 2.11 | 93.8 | |||||||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | 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 | 2 | 58.72 | 19746 | 18017 | 978 | 96.2 | 0.19279 | 0.19011 | 0.24254 | RANDOM | 22.425 | ||||||
| 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] | |
| 0.39 | 0.39 | -0.78 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 38.084 |
| r_dihedral_angle_3_deg | 15.607 |
| r_dihedral_angle_4_deg | 14.121 |
| r_dihedral_angle_1_deg | 5.768 |
| r_scangle_it | 3.308 |
| r_scbond_it | 2.312 |
| r_angle_refined_deg | 1.663 |
| r_mcangle_it | 1.384 |
| r_mcbond_it | 1.191 |
| r_angle_other_deg | 0.951 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 1797 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 223 |
| Heterogen Atoms | 32 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| ADSC | data collection |
| MOLREP | phasing |
| REFMAC | refinement |
| MOSFLM | data reduction |
| SCALA | data scaling |
