4AN3
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 | 7.9 | 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 = 108.659 | α = 90 |
| b = 108.659 | β = 90 |
| c = 50.113 | 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 | MARMOSAIC 325 mm CCD | MIRRORS | 2005-03-31 | M | SINGLE WAVELENGTH | |||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | SSRL BEAMLINE BL11-1 | SSRL | BL11-1 | |
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 | 2.1 | 44.23 | 99.5 | 0.07 | 8.1 | 3.2 | 19901 | 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 | 2.1 | 2.18 | 100 | 0.46 | 2.2 | 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 | R-Free | R-Free Selection Details | Mean Isotropic B | ||||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | UNPUBLISHED MEK1-ATP STRUCTURE | 2.1 | 44.22 | 18755 | 1021 | 99.37 | 0.22865 | 0.22574 | 0.28311 | RANDOM | 44.537 | ||||||
| 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] | |
| -1.99 | -0.99 | -1.99 | 2.98 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 34.931 |
| r_dihedral_angle_4_deg | 18.065 |
| r_dihedral_angle_3_deg | 17.791 |
| r_dihedral_angle_1_deg | 7.106 |
| r_scangle_it | 4.385 |
| r_scbond_it | 3.035 |
| r_angle_refined_deg | 2.1 |
| r_mcangle_it | 1.861 |
| r_mcbond_it | 1.105 |
| r_nbtor_refined | 0.315 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2191 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 88 |
| Heterogen Atoms | 58 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| d*TREK | data reduction |
| d*TREK | data scaling |
| MOLREP | phasing |
