4AJW
Discovery and Optimization of New Benzimidazole- and Benzoxazole-Pyrimidone Selective PI3KBeta Inhibitors for the Treatment of Phosphatase and TENsin homologue (PTEN)-Deficient Cancers
X-RAY DIFFRACTION
Crystallization
Crystalization Experiments | ||||
---|---|---|---|---|
ID | Method | pH | Temperature | Details |
1 | 6.5 | 14-16% PEG 8000 28-32% ETHYLENE GLYCOL 100 MM CARBOXYLIC ACIDS 100 MM MES/IMIDAZOLE, PH 6.5 |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.8 | 56 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 63.4 | α = 90 |
b = 220.47 | β = 113.87 |
c = 78.26 | γ = 90 |
Symmetry | |
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Space Group | P 1 21 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 PILATUS 6M | MIRRORS | 2011-04-26 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
---|---|---|---|---|---|
ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | ESRF BEAMLINE ID29 | ESRF | ID29 |
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 | 2.8 | 71.6 | 98.4 | 0.07 | 10.1 | 3.3 | 47547 | 2 | 84.98 |
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 | 2.8 | 2.87 | 99.5 | 0.47 | 2.4 | 3.4 |
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-Work | R-Free | R-Free Selection Details | Mean Isotropic B | |||||||
X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | PDB ENTRY 2WXF | 2.8 | 71.57 | 47377 | 2433 | 98.36 | 0.252 | 0.277 | RANDOM | 74.83 |
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] | |
-11.0778 | 1.6752 | 3.0863 | 7.9916 |
RMS Deviations | |
---|---|
Key | Refinement Restraint Deviation |
t_other_torsion | 20.33 |
t_omega_torsion | 1.44 |
t_angle_deg | 0.87 |
t_bond_d | 0.007 |
t_dihedral_angle_d | |
t_incorr_chiral_ct | |
t_pseud_angle | |
t_trig_c_planes | |
t_gen_planes | |
t_it |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 12514 |
Nucleic Acid Atoms | |
Solvent Atoms | 34 |
Heterogen Atoms | 48 |
Software
Software | |
---|---|
Software Name | Purpose |
BUSTER-TNT | refinement |
XDS | data reduction |
SCALA | data scaling |
MOLREP | phasing |