Crystal Structure of rat Autotaxin in complex with N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-6-(oxetan-3-ylsulfonyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-2-amine, i.e. SMILES Clc1cc2c(cc1)C[C@@H](C2)Nc1ncc2CN(Cc2n1)S(=O)(=O)C1COC1 with IC50=0.0214337 microM
X-RAY DIFFRACTION
Crystallization
Crystalization Experiments | ||||
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ID | Method | pH | Temperature | Details |
1 | VAPOR DIFFUSION, SITTING DROP | 4.5 | 293 | 15.3 mg/mL protein in 20mM BICINE/NaOH pH8.5, 150mM NaCl, 0.02% NaN3 mixed 50-70% with 50-30% reservoir consisting of 11-17% PEG3350, 0.1M Na-acetate pH4.5, 0.2M Ca-acetate, total volume 200nL |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.34 | 47.33 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 83.577 | α = 90 |
b = 91.265 | β = 90 |
c = 119.204 | γ = 90 |
Symmetry | |
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Space Group | P 21 21 21 |
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 | PSI PILATUS 6M | 2018-11-25 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
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ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | SLS BEAMLINE X10SA | 1.000000 | SLS | X10SA |
Data Collection
Overall | |||||||||||||||||||
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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 | 1.62 | 72.47 | 99.9 | 0.13 | 9.65 | 6.645 | 116219 | 29.63 |
Highest Resolution Shell | |||||||||||||||||||
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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 | 1.62 | 1.66 | 100 | 2.353 | 0.77 | 6.77 |
Refinement
Statistics | |||||||||||||||||||
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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 | INHOUSE MODEL | 1.62 | 72.47 | 88905 | 4649 | 80.7 | 0.168 | 0.166 | 0.1766 | 0.207 | 0.2156 | RANDOM | 22.81 |
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] | |
0.06 | 0.02 | -0.09 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
r_dihedral_angle_2_deg | 30.587 |
r_dihedral_angle_1_deg | 24.484 |
r_dihedral_angle_4_deg | 16.172 |
r_dihedral_angle_3_deg | 12.879 |
r_mcangle_it | 3.778 |
r_mcbond_it | 2.606 |
r_mcbond_other | 2.589 |
r_angle_refined_deg | 1.937 |
r_angle_other_deg | 1.481 |
r_chiral_restr | 0.105 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 6500 |
Nucleic Acid Atoms | |
Solvent Atoms | 658 |
Heterogen Atoms | 173 |
Software
Software | |
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Software Name | Purpose |
REFMAC | refinement |
XSCALE | data scaling |
PDB_EXTRACT | data extraction |
XDS | data reduction |
PHASER | phasing |