5J7B
The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, GSK583 complex
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION | 7 | 293 | 100mM Mes pH7, 12% PEG 400, 250mM CaCl2. Crystals soaked in compound for 2 hours. |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 3.61 | 65.91 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 132.381 | α = 90 |
| b = 132.381 | β = 90 |
| c = 107.28 | γ = 120 |
| Symmetry | |
|---|---|
| Space Group | P 32 2 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 | CCD | ADSC QUANTUM 315r | 2011-01-20 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | DIAMOND BEAMLINE I03 | 0.95 | Diamond | I03 |
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 | 2.53 | 78.33 | 99.9 | 0.095 | 12.9 | 6 | 36582 | ||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||||
| 1 | 2.53 | 2.67 | 100 | 0.385 | 4 | 6 | |||||||||||||
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 | FOURIER SYNTHESIS | THROUGHOUT | 5ar4 | 2.53 | 20 | 34651 | 1825 | 99.6 | 0.18235 | 0.17973 | 0.23255 | RANDOM | 70.473 | ||||||
| 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] | |
| 1.14 | 0.57 | 1.14 | -3.71 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 32.159 |
| r_long_range_B_refined | 12.859 |
| r_dihedral_angle_3_deg | 10.358 |
| r_mcangle_it | 9.325 |
| r_dihedral_angle_4_deg | 8.139 |
| r_scbond_it | 6.97 |
| r_mcbond_it | 6.198 |
| r_dihedral_angle_1_deg | 3.099 |
| r_angle_refined_deg | 1.298 |
| r_chiral_restr | 0.102 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 4470 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 257 |
| Heterogen Atoms | 56 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| MOSFLM | data reduction |
| SCALA | data scaling |
| REFMAC | phasing |
