Fragment-Based Discovery of the Pyrazol-4-yl urea (AT9283), a Multi- targeted Kinase Inhibitor with Potent Aurora Kinase Activity
X-RAY DIFFRACTION
Crystallization
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 1.99 | 38 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 53.57 | α = 90 |
| b = 71.823 | β = 90 |
| c = 72.476 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 21 21 21 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | M | SINGLE WAVELENGTH | |||||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | ROTATING ANODE | ||||
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 | 2.15 | 35 | 98 | 0.1 | 3.1 | 2.5 | 15441 | 2 | |||||||||||
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 (Depositor) | R-Work (DCC) | R-Free (Depositor) | R-Free (DCC) | R-Free Selection Details | Mean Isotropic B | ||||
| X-RAY DIFFRACTION | OTHER | THROUGHOUT | NONE | 2.15 | 35 | 15441 | 799 | 98 | 0.263 | 0.263 | 0.34 | 0.308 | 0.38 | RANDOM | |||||
| Temperature Factor Modeling | ||||||
|---|---|---|---|---|---|---|
| Anisotropic B[1][1] | Anisotropic B[2][2] | Anisotropic B[3][3] | ||||
| 8.311 | -15.48 | 7.169 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| c_angle_deg | 1.37 |
| c_bond_d | 0.007 |
| c_bond_d_na | |
| c_bond_d_prot | |
| c_angle_d | |
| c_angle_d_na | |
| c_angle_d_prot | |
| c_angle_deg_na | |
| c_angle_deg_prot | |
| c_dihedral_angle_d | |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2278 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 221 |
| Heterogen Atoms | 23 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| CNS | refinement |
