Structure-based design of a new series of N-piperidin-3-ylpyrimidine-5-carboxamides as renin inhibitors
X-RAY DIFFRACTION
Crystallization
| Crystalization Experiments | ||||
|---|---|---|---|---|
| ID | Method | pH | Temperature | Details |
| 1 | VAPOR DIFFUSION, SITTING DROP | 7.9 | 293 | 23% PEG600, 0.06M citrate, 0.04M citric acid |
| Crystal Properties | |
|---|---|
| Matthews coefficient | Solvent content |
| 3.02 | 59.33 |
Crystal Data
| Unit Cell | |
|---|---|
| Length ( Å ) | Angle ( ˚ ) |
| a = 139.192 | α = 90 |
| b = 139.192 | β = 90 |
| c = 139.192 | γ = 90 |
| Symmetry | |
|---|---|
| Space Group | P 21 3 |
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 | ADSC QUANTUM 4r | 2006-01-21 | M | SINGLE WAVELENGTH | ||||||
| Radiation Source | |||||
|---|---|---|---|---|---|
| ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
| 1 | SYNCHROTRON | ALS BEAMLINE 5.0.3 | 1.0 | ALS | 5.0.3 |
Data Collection
| Overall | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | 50.01 | 99.9 | 0.07 | 11.2 | 4.3 | 40166 | ||||||||||||
| 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 | 100 | 0.506 | 4.2 | ||||||||||||||
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 (Depositor) | R-Work (DCC) | R-Free (Depositor) | R-Free (DCC) | R-Free Selection Details | Mean Isotropic B | |||||
| X-RAY DIFFRACTION | MOLECULAR REPLACEMENT | THROUGHOUT | 2.3 | 50.01 | 37946 | 1998 | 99.38 | 0.1943 | 0.1921 | 0.1963 | 0.2367 | 0.2363 | RANDOM | 42.034 | |||||
| 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] | |
| RMS Deviations | |
|---|---|
| Key | Refinement Restraint Deviation |
| r_dihedral_angle_2_deg | 34.183 |
| r_dihedral_angle_3_deg | 12.971 |
| r_dihedral_angle_4_deg | 12.572 |
| r_dihedral_angle_1_deg | 7.086 |
| r_mcangle_it | 1.884 |
| r_angle_refined_deg | 1.277 |
| r_mcbond_it | 1.147 |
| r_mcbond_other | 1.139 |
| r_angle_other_deg | 0.854 |
| r_chiral_restr | 0.07 |
| Non-Hydrogen Atoms Used in Refinement | |
|---|---|
| Non-Hydrogen Atoms | Number |
| Protein Atoms | 5097 |
| Nucleic Acid Atoms | |
| Solvent Atoms | 379 |
| Heterogen Atoms | 156 |
Software
| Software | |
|---|---|
| Software Name | Purpose |
| HKL-2000 | data collection |
| HKL-2000 | data scaling |
| MOLREP | phasing |
| REFMAC | refinement |
| PDB_EXTRACT | data extraction |
| HKL-2000 | data reduction |
