2X8I
Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead Exploration
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 6.5 | HANGING DROP 3 UL PLUS 3UL PROTEIN: 7MG/ML, 2MM COMPOUND, 25MM TRIS PH7.5, 500MM NACL, 5% GLYCEROL. 5MM DTT WELL: 16-22% (W/V) PEG3350, 150MM AMMONIUM SULPHATE AND 100 MM BES PH 6.5 | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.28 | 45.65 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 41.255 | α = 90 |
| b = 70.9 | β = 90 |
| c = 104.241 | 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 | CCD | MARRESEARCH | 2002-08-20 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | EMBL/DESY, HAMBURG BEAMLINE X13 | EMBL/DESY, HAMBURG | X13 | |
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 | 1.92 | 31.16 | 94.3 | 0.08 | 14 | 5.8 | 22530 | 2 | |||||||||||
| 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 | 1.92 | 2.02 | 89.4 | 0.29 | 5.6 | 5.4 | |||||||||||||
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 | PDB ENTRY 2X8D | 1.92 | 31.16 | 21383 | 1147 | 93.59 | 0.1894 | 0.1876 | 0.22368 | RANDOM | 15.693 | ||||||
| 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] | |
| -1.49 | 1.65 | -0.17 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 37.479 |
| r_dihedral_angle_4_deg | 15.719 |
| r_dihedral_angle_3_deg | 12.344 |
| r_dihedral_angle_1_deg | 5.158 |
| r_scangle_it | 2.124 |
| r_angle_other_deg | 1.825 |
| r_scbond_it | 1.275 |
| r_angle_refined_deg | 1.269 |
| r_mcangle_it | 0.937 |
| r_mcbond_it | 0.503 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2091 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 241 |
| Heterogen Atoms | 38 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| MOSFLM | data reduction |
| SCALA | data scaling |
| AMoRE | phasing |
