6USZ
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 | 4.6 | 293 | 23% PEG8K 0.1M NaCitrate pH 4.6 0.2M Amm Acetate |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.34 | 47.53 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( ? ) | Angle ( ? ) |
| a = 39.769 | ¦Á = 90 |
| b = 50.9 | ¦Â = 90 |
| c = 89.649 | ¦Ã = 90 |
| Symmetry | |
|---|---|
| Space Group | P 21 21 21 |
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 | 2017-05-24 | 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) | 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 | 2.03 | 30 | 93.8 | 0.117 | 11.16 | 6.46 | 12000 | ||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rpim I (All) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||
| 1 | 2.03 | 2.08 | 92.4 | 0.249 | 0.115 | 6.1 | 6.6 | ||||||||||||
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 | Mean Isotropic B | |||||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | 4L8G.pdb | 2.03 | 29.749 | 11476 | 567 | 93.248 | 0.136 | 0.1315 | 0.2257 | 16.29 | |||||||
| 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] | |
| 0.322 | -0.666 | 0.344 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 34.848 |
| r_dihedral_angle_4_deg | 21.138 |
| r_dihedral_angle_3_deg | 15.42 |
| r_dihedral_angle_1_deg | 6.514 |
| r_lrange_it | 5.479 |
| r_scangle_it | 5.165 |
| r_scbond_it | 4.37 |
| r_rigid_bond_restr | 3.007 |
| r_mcangle_it | 2.825 |
| r_mcbond_it | 2.254 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 1354 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 120 |
| Heterogen Atoms | 70 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| iMOSFLM | data reduction |
| SCALEPACK | data scaling |
| PHASER | phasing |
