4I0E
Design and Synthesis of Thiophene Dihydroisoquinolins as Novel BACE-1 Inhibitors
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 5.3 | 277 | BACE was concentrated to 10mg/ml in 100 mM borate pH 8.5, 9% PEG 8000, 100mM sodium acetate and 10mM ZnCl2, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 2.14 | 42.52 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 75.062 | α = 90 |
| b = 103.335 | β = 90 |
| c = 100.306 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | C 2 2 21 |
Diffraction
| Diffraction Experiment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
| 1 | 1 | x-ray | 100 | CCD | RIGAKU SATURN 944+ | 2011-01-01 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | ROTATING ANODE | RIGAKU MICROMAX-007 HF | 1.5418 | ||
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ID # | Resolution (High) | Resolution (Low) | Percent Possible (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 | 1.7 | 60 | 92 | 39688 | 41475 | 1 | 1 | ||||||||||||
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 | 1.7 | 60 | 39393 | 2083 | 84.79 | 0.23346 | 0.23003 | 0.29957 | RANDOM | 36.853 | |||||||
| 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] | |
| -0.8 | -1.14 | 1.94 | ||||
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 33.939 |
| r_dihedral_angle_4_deg | 18.086 |
| r_dihedral_angle_3_deg | 16.085 |
| r_angle_other_deg | 8.307 |
| r_dihedral_angle_1_deg | 8.237 |
| r_scangle_it | 4.649 |
| r_scbond_it | 3.024 |
| r_mcangle_it | 2.19 |
| r_angle_refined_deg | 2.13 |
| r_mcbond_it | 1.303 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 3099 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 220 |
| Heterogen Atoms | 33 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| StructureStudio | data collection |
| MOLREP | phasing |
| REFMAC | refinement |
