Structure of EGFR_D770_N771insNPG/V948R in complex with covalent inhibitor Osimertinib.
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 4LRM | |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 293 | 20% PEG 8000, 200mM Ammonium Citrate, 100mM MES pH 6.5 | |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.28 | 46.05 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 60.659 | α = 90 |
| b = 132.1 | β = 91.4 |
| c = 85.805 | γ = 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 | CCD | ADSC QUANTUM 4r | 2019-05-08 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | ALS BEAMLINE 5.0.3 | 0.987 | ALS | 5.0.3 |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | 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 | 2.94 | 49.01 | 99.3 | 0.269 | 0.313 | 0.16 | 0.989 | 4 | 3.8 | 28583 | |||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rrim I (All) | Rpim I (All) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||
| 1 | 2.94 | 3.12 | 99.1 | 2.073 | 2.412 | 1.227 | 0.409 | 3.8 | |||||||||||
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 (Depositor) | R-Work (DCC) | R-Free (Depositor) | R-Free (DCC) | R-Free Selection Details | Mean Isotropic B | ||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | 4LRM | 3.1 | 49.01 | 22057 | 1148 | 94.2 | 0.241 | 0.2377 | 0.24 | 0.3053 | 0.31 | RANDOM | 84.016 | ||||
| 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] | |
| 6.76 | -3.32 | -2.95 | -3.63 | |||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 34.192 |
| r_dihedral_angle_3_deg | 17.11 |
| r_dihedral_angle_4_deg | 14.283 |
| r_dihedral_angle_1_deg | 6.27 |
| r_angle_refined_deg | 0.892 |
| r_chiral_restr | 0.07 |
| r_gen_planes_refined | 0.003 |
| r_bond_refined_d | 0.002 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 9049 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 153 |
| Heterogen Atoms | 185 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| Aimless | data scaling |
| REFMAC | refinement |
| PDB_EXTRACT | data extraction |
| DENZO | data reduction |
| PHASER | phasing |
