Optimization of potent and selective ATM inhibitors suitable for a proof-of-concept study in Huntington's disease models
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 3LS8 | |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 7 | 293 | 1.4 M Sodium Malonate pH 7.0, 0.1 M Bis-Tris Propane pH 7.0 |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 3.09 | 60.13 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 84.17 | α = 90 |
| b = 167.17 | β = 90 |
| c = 61.5 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 21 21 2 |
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 6M | 2016-04-09 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | DIAMOND BEAMLINE I03 | 0.9763 | Diamond | I03 |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | 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 | 2.09 | 83.58 | 99.5 | 0.084 | 0.093 | 0.037 | 0.999 | 12.8 | 6 | 51984 | |||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||
| 1 | 2.09 | 2.13 | 95.4 | 0.82 | 0.978 | 0.521 | 0.645 | 1.2 | 3.2 | ||||||||||
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 | MOLECULAR REPLACEMENT | THROUGHOUT | 3LS8 | 2.09 | 83.58 | 49365 | 2561 | 99.34 | 0.19096 | 0.18869 | 0.2 | 0.23556 | 0.24 | RANDOM | 42.587 | ||||
| Temperature Factor Modeling | ||||||
|---|---|---|---|---|---|---|
| Anisotropic B[1][1] | Anisotropic B[2][2] | Anisotropic B[3][3] | ||||
| 4.09 | -0.21 | -3.87 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 35.464 |
| r_dihedral_angle_4_deg | 21.156 |
| r_dihedral_angle_3_deg | 16.008 |
| r_long_range_B_other | 7.595 |
| r_long_range_B_refined | 7.591 |
| r_scangle_other | 6.184 |
| r_dihedral_angle_1_deg | 6.031 |
| r_mcangle_it | 4.433 |
| r_mcangle_other | 4.433 |
| r_scbond_it | 4.013 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 4418 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 179 |
| Heterogen Atoms | 37 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| xia2 | data reduction |
| Aimless | data scaling |
| PHASER | phasing |
