5K7K
Design and Optimization of Biaryl Ether Aryl Sulfonamides as Selective Inhibitors of NaV1.7: Discovery of Clinical Candidate PF-05089771
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION | 8.5 | 293 | 100mM Hepes at 8.5 with 2% Peg 4K. crystallizer Alec Tucker Cryoprotectand 40% peg 4K |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.53 | 51.38 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 91.69 | α = 90 |
| b = 91.69 | β = 90 |
| c = 169.88 | γ = 120 |
| Symmetry | |
|---|---|
| Space Group | H 3 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 293 | CCD | ADSC QUANTUM 315 | 2008-01-22 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | ESRF BEAMLINE ID14-4 | 1 | ESRF | ID14-4 |
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 | 2.3 | 17 | 98.6 | 3 | 6 | 22151 | |||||||||||||
| 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 | 2.3 | 2.359 | 99.89 | ||||||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | 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 | 1R9O | 2.3 | 17.33 | 22151 | 1192 | 98.61 | 0.22681 | 0.22437 | 0.27194 | RANDOM | 59.48 | ||||||
| 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 | 0.01 | 0.01 | -0.04 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 40.305 |
| r_dihedral_angle_3_deg | 19.524 |
| r_dihedral_angle_4_deg | 17.9 |
| r_long_range_B_refined | 11.127 |
| r_long_range_B_other | 11.124 |
| r_mcangle_it | 5.965 |
| r_mcangle_other | 5.963 |
| r_scangle_other | 5.842 |
| r_mcbond_it | 3.837 |
| r_mcbond_other | 3.837 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 3646 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 37 |
| Heterogen Atoms | 73 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| HKL-2000 | data reduction |
| HKL-2000 | data scaling |
| PHASER | phasing |
