4AN9
Crystal structures of human MEK1 with carboxamide-based allosteric inhibitor XL518 (GDC-0973), or related analogs.
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 8.9 | SITTING DROP VAPOR-DIFFUSION VS. 26.5 % PEG-2000 MME, 0.1 M TRIMETHYLAMINE N-OXIDE, 0.1 M TRIS (PH 8.9) | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.32 | 47 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 108.653 | α = 90 |
| b = 108.653 | β = 90 |
| c = 49.394 | γ = 120 |
| Symmetry | |
|---|---|
| Space Group | P 61 |
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 | ADSC QUANTUM 315r | FLAT MIRROR, RH COATED | 2005-05-10 | M | SINGLE WAVELENGTH | |||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | SSRL BEAMLINE BL9-1 | SSRL | BL9-1 | |
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 | 49.39 | 99.8 | 0.12 | 11.3 | 5.4 | 8366 | 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 | 2.8 | 2.95 | 100 | 0.82 | 2.3 | 5.5 | |||||||||||||
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 | UNPUBLISHED MEK1-ATP COMPLEX | 2.8 | 49.4 | 7922 | 429 | 99.67 | 0.20522 | 0.19974 | 0.31259 | RANDOM | 50.373 | ||||||
| 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] | |
| -2.92 | -1.46 | -2.92 | 4.38 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 36.965 |
| r_dihedral_angle_3_deg | 21.074 |
| r_dihedral_angle_4_deg | 20.92 |
| r_dihedral_angle_1_deg | 7.451 |
| r_scangle_it | 3.701 |
| r_scbond_it | 2.261 |
| r_angle_refined_deg | 2.26 |
| r_mcangle_it | 1.499 |
| r_mcbond_it | 0.813 |
| r_nbtor_refined | 0.331 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2198 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 5 |
| Heterogen Atoms | 56 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| MOSFLM | data reduction |
| SCALA | data scaling |
| MOLREP | phasing |
