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 |
2.1 | 42 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 63.542 | α = 90 |
b = 90.729 | β = 109.519 |
c = 77.678 | γ = 90 |
Symmetry | |
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Space Group | P 1 21 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 | 1.95 | 45.36 | 99.1 | 0.095 | 0.114 | 0.064 | 0.995 | 8.7 | 3.1 | 60013 |
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 | 1.95 | 2 | 99.4 | 0.592 | 3 |
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 | 1.95 | 38.592 | 59988 | 2898 | 99.023 | 0.175 | 0.1742 | 0.175 | 0.2012 | 0.2018 | RANDOM | 31.492 |
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] | |
-0.445 | -0.572 | 1.905 | -0.843 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
r_dihedral_angle_2_deg | 19.272 |
r_dihedral_angle_6_deg | 15.862 |
r_dihedral_angle_3_deg | 13.337 |
r_dihedral_angle_1_deg | 9.324 |
r_lrange_it | 7.934 |
r_lrange_other | 7.894 |
r_scangle_it | 5.434 |
r_scangle_other | 5.434 |
r_scbond_it | 3.567 |
r_scbond_other | 3.567 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 6292 |
Nucleic Acid Atoms | |
Solvent Atoms | 364 |
Heterogen Atoms | 272 |
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 |