6GDM
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 | 35.0%w/v MPEG 2000, 0.2M (NH4)2SO4, 0.1M HEPES/NaOHpH=7.2, 0.02M Mercaptoethanol |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.3 | 46.54 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( ? ) | Angle ( ? ) |
| a = 48.722 | ¦Á = 90 |
| b = 70.69 | ¦Â = 109.45 |
| c = 60.615 | ¦Ã = 90 |
| Symmetry | |
|---|---|
| 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 | CCD | RIGAKU SATURN 944+ | 2013-04-10 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | ROTATING ANODE | RIGAKU FR-X | 1.54178 | ||
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | Rrim I (All) | 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 | 1.91 | 57.156 | 97.7 | 0.051 | 14 | 2.7 | 30330 | ||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | Rrim I (All) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||||
| 1 | 1.91 | 1.97 | 83.6 | 0.483 | 1.9 | ||||||||||||||
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 | 1.91 | 27.47 | 28055 | 1527 | 97.53 | 0.18515 | 0.18204 | 0.24265 | RANDOM | 33.486 | |||||||
| 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] | |
| -0.93 | 0.02 | 0.84 | 0.07 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 37.082 |
| r_dihedral_angle_4_deg | 19.151 |
| r_dihedral_angle_3_deg | 14.637 |
| r_dihedral_angle_1_deg | 6.551 |
| r_long_range_B_refined | 5.585 |
| r_long_range_B_other | 5.542 |
| r_scbond_it | 2.707 |
| r_scbond_other | 2.706 |
| r_mcbond_it | 2.069 |
| r_mcbond_other | 2.057 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2826 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 394 |
| Heterogen Atoms | 58 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| XDS | data reduction |
| SCALA | data scaling |
| REFMAC | phasing |
