3QI1
Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors
X-RAY DIFFRACTION
Crystallization
Crystalization Experiments | ||||
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ID | Method | pH | Temperature | Details |
1 | 4.6 | 295 | BACE PROTEIN AT 10MG/ML IN 100MM SODIUM BORATE BUFFER PH 8.5. 1MM COMPOUND ADDED TO PROTEIN AND INCUBATED AT 4 C FOR 3 HOURS. HANGING DROP PLATES SET UP WITH RESERVOIR SOLUTION CONTAINING 4% PEG 8000, 100MM SODIUM ACETATE PH 4.6 THE DROPS WERE MIXED WITH 1:1 (V/V) RATIO OF PROTEIN/COMPOUND TO RESERVOIR AND INCUBATED AT ROOM TEMPERATURE FOR 2 WEEKS. VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 295K |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.41 | 48.96 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 72.174 | α = 90 |
b = 75.506 | β = 90 |
c = 80.236 | 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 | IMAGE PLATE | RIGAKU RAXIS HTC | MIRRORS | 2010-07-30 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
---|---|---|---|---|---|
ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | ROTATING ANODE | RIGAKU MICROMAX-007 |
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 | 2.3 | 25.69 | 96.2 | 0.086 | 9.2 | 3.89 | 19292 | 1 |
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 | 2.3 | 2.38 | 99.8 | 0.406 | 2.3 | 3.86 |
Refinement
Statistics | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction ID | Structure Solution Method | Cross Validation method | Resolution (High) | Resolution (Low) | 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 | 2.3 | 25.69 | 18250 | 986 | 95.8 | 0.20191 | 0.19837 | 0.26878 | RANDOM | 29.646 |
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] | |
0.9 | -0.8 | -0.11 |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
r_dihedral_angle_2_deg | 31.24 |
r_dihedral_angle_4_deg | 18.997 |
r_dihedral_angle_3_deg | 17.869 |
r_dihedral_angle_1_deg | 7.671 |
r_scangle_it | 4.299 |
r_scbond_it | 2.756 |
r_mcangle_it | 2.025 |
r_angle_refined_deg | 1.867 |
r_mcbond_it | 1.098 |
r_chiral_restr | 0.126 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 2986 |
Nucleic Acid Atoms | |
Solvent Atoms | 214 |
Heterogen Atoms | 36 |
Software
Software | |
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Software Name | Purpose |
MOLREP | phasing |
REFMAC | refinement |
CrystalClear | data reduction |
CrystalClear | data scaling |