4CMU
Structure of the Human Anaplastic Lymphoma Kinase in Complex with the inhibitor (10R)-7-amino-12-fluoro-1,3,10,16-tetramethyl-16,17-dihydro- 1H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11)benzoxadiazacyclotetradecin-15(10H)-one
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, HANGING DROP | 5.5 | 286 | HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 13-15 MG/ML)CONTAINING 0.001M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.15M AMMONIUM SULFATE, 9-10.5% MONOMETHYLETHER PEG5K AND 0.1M MES IN THE PH RANGE 5.3-6.5. |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.1 | 41 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 51.83 | α = 90 |
| b = 57.3 | β = 90 |
| c = 104.94 | 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 | 87 | PIXEL | DECTRIS PILATUS 6M | 2011-09-25 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | DIAMOND BEAMLINE I04-1 | Diamond | I04-1 | |
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 | 1.68 | 57.3 | 99.9 | 0.57 | 18.4 | 6.6 | 68428 | 1 | 19.3 | ||||||||||
| Highest Resolution Shell | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||||
| 1 | 1.68 | 1.72 | 99.9 | 0.85 | 2.6 | 6.8 | |||||||||||||
Refinement
| Statistics | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | Number Reflections (All) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (Observed) | R-Work | R-Free | R-Free Selection Details | Mean Isotropic B | |||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | PDB ENTRY 2XP2 | 1.8 | 52.47 | 55597 | 53583 | 1591 | 95.8 | 0.206 | 0.206 | 0.227 | RANDOM | 29.7 | |||||
| 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] | |
| -1.57 | -6.6 | 8.17 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| c_dihedral_angle_d | 19.2 |
| c_scangle_it | 3.34 |
| c_scbond_it | 2.24 |
| c_mcangle_it | 2.23 |
| c_mcbond_it | 1.41 |
| c_angle_deg | 0.8 |
| c_improper_angle_d | 0.67 |
| c_bond_d | 0.005 |
| c_bond_d_na | |
| c_bond_d_prot | |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 2314 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 240 |
| Heterogen Atoms | 29 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| CNX | refinement |
| XDS | data reduction |
| xia2 | data reduction |
| SCALA | data scaling |
| CNX | phasing |
