6G93
Fragment-based discovery of a highly potent, orally bioavailable inhibitor which modulates the phosphorylation and catalytic activity of ERK1/2
X-RAY DIFFRACTION
Crystallization
Crystalization Experiments | ||||
---|---|---|---|---|
ID | Method | pH | Temperature | Details |
1 | VAPOR DIFFUSION, SITTING DROP | 7.2 | 293 | 0.1M HEPES/NaOHpH=7.2, 34.0%w/v MPEG 2000, 0.02M Mercaptoethanol, 0.2M (NH4)2SO4 |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.31 | 46.84 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 48.812 | α = 90 |
b = 70.514 | β = 110.3 |
c = 60.994 | 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-F | 2014-12-01 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
---|---|---|---|---|---|
ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | DIAMOND BEAMLINE I02 | 0.97944 | Diamond | I02 |
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 | 1.67 | 43.95 | 99.7 | 0.03 | 19.4 | 3.3 | 45501 | 31.71 |
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 | 1.67 | 1.68 | 99.8 | 1.166 |
Refinement
Statistics | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction ID | Structure Solution Method | Cross Validation method | 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 | 1.67 | 43.95 | 45237 | 2313 | 99.7 | 0.173 | 0.171 | 0.213 | RANDOM | 42.519 |
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] | |
0.7077 | 1.6614 | -1.1563 | 0.4486 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
t_other_torsion | 14.7 |
t_omega_torsion | 6.23 |
t_angle_deg | 1.11 |
t_bond_d | 0.013 |
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 | 2790 |
Nucleic Acid Atoms | |
Solvent Atoms | 402 |
Heterogen Atoms | 59 |
Software
Software | |
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Software Name | Purpose |
BUSTER | refinement |
XDS | data reduction |
Aimless | data scaling |
BUSTER | phasing |