6UT0
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 | 293 | 32% PEG 4K 0.1M NaOAc (unbuffered) 8% 2-Propanol | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.12 | 41.92 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( ? ) | Angle ( ? ) |
| a = 74.918 | ¦Á = 90 |
| b = 61.8 | ¦Â = 111.37 |
| c = 76.05 | ¦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 | PIXEL | DECTRIS PILATUS 2M | Osmic confocal mirrors | 2017-11-29 | 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 | 1.94 | 30 | 96.3 | 0.076 | 15.8 | 6.45 | 47734 | ||||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||
| 1 | 1.94 | 1.99 | 92.8 | 0.21 | 0.235 | 0.102 | 5.7 | 5.4 | |||||||||||
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 | 1.94 | 28.321 | 46376 | 2375 | 96.318 | 0.177 | 0.1746 | 0.222 | 20.445 | |||||||
| 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] | |
| -0.921 | 0.595 | -0.122 | 0.441 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 33.299 |
| r_dihedral_angle_4_deg | 21.5 |
| r_dihedral_angle_3_deg | 14.629 |
| r_dihedral_angle_other_3_deg | 11.309 |
| r_dihedral_angle_1_deg | 6.558 |
| r_lrange_it | 5.186 |
| r_lrange_other | 5.12 |
| r_scangle_other | 3.595 |
| r_scangle_it | 3.541 |
| r_mcangle_it | 2.453 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 5413 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 446 |
| Heterogen Atoms | 288 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| REFMAC | refinement |
| iMOSFLM | data reduction |
| SCALA | data scaling |
| PHENIX | phasing |
