Crystal Structure of Autotaxin (ENPP2) with Type VI Inhibitor, a Novel Class of Inhibitors with Three-Point Lock Binding Mode
X-RAY DIFFRACTION
Starting Model(s)
Initial Refinement Model(s) | |||
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Type | Source | Accession Code | Details |
experimental model | PDB | 2XR9 |
Crystallization
Crystalization Experiments | ||||
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ID | Method | pH | Temperature | Details |
1 | VAPOR DIFFUSION, HANGING DROP | 293 | ATX was incubated with each screened compound at a 1:10 (protein:compound) ratio for at least 30 minutes. Crystals were grown for at least 7 days in a 24-well optimization screen: 18 to 20% PEG 3350, 0.1 to 0.4 M NaSCN, and 0.1 to 0.4 M NH4I. |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.4 | 48.66 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 53.706 | α = 99.553 |
b = 63.424 | β = 105.153 |
c = 70.306 | γ = 99.268 |
Symmetry | |
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Space Group | P 1 |
Diffraction
Diffraction Experiment | ||||||||||||||
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ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
1 | 1 | x-ray | 100 | PIXEL | DECTRIS PILATUS3 2M | 2021-05-06 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
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ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | ESRF BEAMLINE MASSIF-1 | 0.965459 | ESRF | MASSIF-1 |
Data Collection
Overall | |||||||||||||||||||
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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 | 2.25 | 47.59 | 97.9 | 0.091 | 0.114 | 0.068 | 0.978 | 7.3 | 2.7 | 40044 |
Highest Resolution Shell | |||||||||||||||||||
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ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | |||||||||||
1 | 2.25 | 2.32 | 97.3 | 0.477 | 2.6 |
Refinement
Statistics | |||||||||||||||||||
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Diffraction ID | Structure Solution Method | Cross Validation method | Resolution (High) | Resolution (Low) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (All) | 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 | 2.25 | 47.59 | 40041 | 2025 | 97.864 | 0.179 | 0.1772 | 0.1819 | 0.2102 | 0.2146 | RANDOM | 53.694 |
Temperature Factor Modeling | ||||||
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Anisotropic B[1][1] | Anisotropic B[1][2] | Anisotropic B[1][3] | Anisotropic B[2][2] | Anisotropic B[2][3] | Anisotropic B[3][3] | |
-0.245 | 0.836 | 1.627 | -0.128 | 0.046 | -0.736 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
r_dihedral_angle_2_deg | 23.451 |
r_dihedral_angle_6_deg | 15.297 |
r_dihedral_angle_3_deg | 13.576 |
r_dihedral_angle_1_deg | 10.551 |
r_lrange_it | 8.233 |
r_lrange_other | 8.206 |
r_scangle_it | 4.485 |
r_scangle_other | 4.29 |
r_mcangle_other | 3.235 |
r_mcangle_it | 3.234 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 6305 |
Nucleic Acid Atoms | |
Solvent Atoms | 255 |
Heterogen Atoms | 192 |
Software
Software | |
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Software Name | Purpose |
REFMAC | refinement |
Aimless | data scaling |
MOLREP | phasing |
Coot | model building |
MolProbity | model building |
XDS | data reduction |
PDB-REDO | refinement |