Structure of BTK kinase domain with the second-generation inhibitor acalabrutinib
X-RAY DIFFRACTION
Starting Model(s)
| Initial Refinement Model(s) | |||
|---|---|---|---|
| Type | Source | Accession Code | Details |
| experimental model | PDB | 5P9J | |
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | EVAPORATION | 6.5 | 277 | 20% PEG 3350, 0.1M Bis-tris propane, pH 6.5 and 0.2M sodium bromide |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.25 | 45.37 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 42.921 | α = 90 |
| b = 50.31 | β = 90 |
| c = 123.483 | γ = 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 EIGER2 S 16M | 2022-07-07 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | APS BEAMLINE 24-ID-E | 0.97918 | APS | 24-ID-E |
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 | 1.626 | 46.591 | 82.2 | 0.148 | 0.162 | 0.064 | 0.996 | 1.2 | 5.5 | 28343 | 17.65 | ||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Rpim I (All) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||
| 1 | 1.626 | 1.745 | 21.8 | 1.276 | 0.582 | 0.499 | 1.5 | 5.4 | |||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Resolution (High) | Resolution (Low) | Cut-off Sigma (F) | 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) | Mean Isotropic B | |||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | FREE R-VALUE | 1.7 | 19.74 | 1.34 | 27871 | 1394 | 92.25 | 0.1887 | 0.1866 | 0.19 | 0.2276 | 0.23 | 23.15 | |||||
| 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] | |
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| f_dihedral_angle_d | 12.0686 |
| f_angle_d | 0.4745 |
| f_chiral_restr | 0.0388 |
| f_plane_restr | 0.0032 |
| f_bond_d | 0.0016 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2215 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 267 |
| Heterogen Atoms | 39 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| PHENIX | refinement |
| autoPROC | data processing |
| PHASER | phasing |
| autoPROC | data reduction |
| XDS | data scaling |
| Coot | model building |
