5TQ5
Design and Synthesis of a pan-JAK Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 7.5 | 293 | 0.1 M Hepes, pH 7.5, 0.1 M sodium acetate, 30% PEG-3350 |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.26 | 45.65 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 36.997 | α = 104.11 |
| b = 45.106 | β = 110.08 |
| c = 52.807 | γ = 94.73 |
| Symmetry | |
|---|---|
| Space Group | P 1 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | PIXEL | DECTRIS PILATUS3 R CdTe 300K | 2010-05-01 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | DIAMOND BEAMLINE I04-1 | 1 | Diamond | I04-1 |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge 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 | 2.3 | 40 | 90 | 0.1 | 6.5 | 2 | 11921 | ||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | 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 | THROUGHOUT | 2.3 | 27.31 | 11921 | 663 | 92.61 | 0.28227 | 0.27933 | 0.33246 | RANDOM | 17 | ||||||||
| 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] | |
| -0.06 | 0.02 | 0.03 | -0.02 | 0.07 | 0.01 | |
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 37.902 |
| r_dihedral_angle_4_deg | 21.703 |
| r_dihedral_angle_3_deg | 17.364 |
| r_dihedral_angle_1_deg | 4.848 |
| r_long_range_B_refined | 2.823 |
| r_long_range_B_other | 2.823 |
| r_mcangle_it | 2.095 |
| r_mcangle_other | 2.094 |
| r_scangle_other | 1.573 |
| r_angle_refined_deg | 1.359 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2370 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 34 |
| Heterogen Atoms | 28 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| XDS | data reduction |
| XDS | data scaling |
| PHASER | phasing |
