6USX
Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 4L8G | 4l8g.pdb |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 5.4 | 293 | 29% PEG8K 0.1M NaCitrate pH 5.4 0.2M Amm Acetate |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.82 | 56.37 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( ? ) | Angle ( ? ) |
| a = 88.57 | ¦Á = 90 |
| b = 156.49 | ¦Â = 90 |
| c = 62.98 | ¦Ã = 90 |
| Symmetry | |
|---|---|
| Space Group | C 2 2 2 |
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 2M | Osmic confocal mirrors | 2019-01-30 | M | SINGLE WAVELENGTH | |||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | ROTATING ANODE | RIGAKU FR-E | 1.5418 | ||
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | Rrim I (All) | Rpim 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 | 2.27 | 30 | 84.7 | 0.25 | 0.135 | 9.72 | 3.65 | 32164 | |||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | Rrim I (All) | Rpim I (All) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||
| 1 | 2.27 | 2.42 | 69 | 0.25 | 0.135 | 4.7 | 3.3 | ||||||||||||
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 (All) | R-Work | R-Free | R-Free Selection Details | Mean Isotropic B | ||||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | 4l8g.pdb | 2.27 | 29.51 | 18040 | 980 | 87.31 | 0.191 | 0.1873 | 0.2498 | Random | 46.102 | ||||||
| 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] | |
| -3.266 | -0.484 | 3.75 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 36.579 |
| r_dihedral_angle_4_deg | 16.032 |
| r_dihedral_angle_3_deg | 15.048 |
| r_lrange_other | 8.929 |
| r_lrange_it | 8.798 |
| r_scangle_other | 7.624 |
| r_scangle_it | 7.49 |
| r_dihedral_angle_1_deg | 6.882 |
| r_dihedral_angle_other_3_deg | 5.658 |
| r_mcangle_it | 5.592 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2685 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 75 |
| Heterogen Atoms | 134 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| iMOSFLM | data reduction |
| SCALA | data scaling |
| PHASER | phasing |
