3IVI

Design and Synthesis of Potent BACE-1 Inhibitors with Cellular Activity: Structure-Activity Relationship of P1 Substituents


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, SITTING DROP4.52890.1 M sodium acetate pH 4.5, 20% PEG200 Compound was added to give a final molar access of compound:protein of 2.5:1, VAPOR DIFFUSION, SITTING DROP, temperature 289K
Crystal Properties
Matthews coefficientSolvent content
3.0860.1

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 82.711α = 90
b = 104.48β = 104.83
c = 100.616γ = 90
Symmetry
Space GroupP 1 21 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-rayCCDADSC QUANTUM 315r2004-08-06MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONALS BEAMLINE 8.3.1ALS8.3.1

Data Collection

Overall
ID #Resolution (High)Resolution (Low)Percent Possible (Observed)Net I Over Average Sigma (I)RedundancyNumber Reflections (All)Number Reflections (Observed)Observed Criterion Sigma (F)Observed Criterion Sigma (I)B (Isotropic) From Wilson Plot
12.295.357980379205
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
12.22.257

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodResolution (High)Resolution (Low)Number Reflections (Observed)Number Reflections (R-Free)Percent Reflections (Observed)R-Factor (Observed)R-WorkR-FreeR-Free Selection DetailsMean Isotropic B
X-RAY DIFFRACTIONMOLECULAR REPLACEMENTTHROUGHOUT2.295.3579205416599.250.19640.19470.22893RANDOM35.169
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]
-0.91-1.212.59-2.3
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_1_deg3.54
r_scangle_it2.197
r_angle_refined_deg1.428
r_scbond_it1.301
r_mcangle_it0.981
r_angle_other_deg0.814
r_mcbond_it0.517
r_symmetry_vdw_other0.255
r_nbd_other0.228
r_symmetry_vdw_refined0.226
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_1_deg3.54
r_scangle_it2.197
r_angle_refined_deg1.428
r_scbond_it1.301
r_mcangle_it0.981
r_angle_other_deg0.814
r_mcbond_it0.517
r_symmetry_vdw_other0.255
r_nbd_other0.228
r_symmetry_vdw_refined0.226
r_nbd_refined0.205
r_symmetry_hbond_refined0.137
r_xyhbond_nbd_refined0.133
r_chiral_restr0.087
r_nbtor_other0.082
r_bond_refined_d0.01
r_gen_planes_refined0.004
r_bond_other_d0.002
r_gen_planes_other0.002
r_dihedral_angle_2_deg
r_dihedral_angle_3_deg
r_dihedral_angle_4_deg
r_nbtor_refined
r_xyhbond_nbd_other
r_metal_ion_refined
r_metal_ion_other
r_symmetry_hbond_other
r_symmetry_metal_ion_refined
r_symmetry_metal_ion_other
r_mcbond_other
r_rigid_bond_restr
r_sphericity_free
r_sphericity_bonded
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms8905
Nucleic Acid Atoms
Solvent Atoms235
Heterogen Atoms159

Software

Software
Software NamePurpose
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing