3QI1

Design and synthesis of hydroxyethylamine (hea) BACE-1 inhibitors: prime side chromane-containing inhibitors


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
14.6295BACE 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
Matthews coefficientSolvent content
2.4148.96

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 72.174α = 90
b = 75.506β = 90
c = 80.236γ = 90
Symmetry
Space GroupP 21 21 21

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100IMAGE PLATERIGAKU RAXIS HTCMIRRORS2010-07-30MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1ROTATING ANODERIGAKU MICROMAX-007

Data Collection

Overall
ID #Resolution (High)Resolution (Low)Percent Possible (Observed)R Merge I (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
12.325.6996.20.0869.23.89192921
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)R Merge I (Observed)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
12.32.3899.80.4062.33.86

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 REPLACEMENTTHROUGHOUT2.325.691825098695.80.201910.198370.26878RANDOM29.646
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
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg31.24
r_dihedral_angle_4_deg18.997
r_dihedral_angle_3_deg17.869
r_dihedral_angle_1_deg7.671
r_scangle_it4.299
r_scbond_it2.756
r_mcangle_it2.025
r_angle_refined_deg1.867
r_mcbond_it1.098
r_chiral_restr0.126
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg31.24
r_dihedral_angle_4_deg18.997
r_dihedral_angle_3_deg17.869
r_dihedral_angle_1_deg7.671
r_scangle_it4.299
r_scbond_it2.756
r_mcangle_it2.025
r_angle_refined_deg1.867
r_mcbond_it1.098
r_chiral_restr0.126
r_bond_refined_d0.022
r_gen_planes_refined0.01
r_bond_other_d
r_angle_other_deg
r_gen_planes_other
r_nbd_refined
r_nbd_other
r_nbtor_refined
r_nbtor_other
r_xyhbond_nbd_refined
r_xyhbond_nbd_other
r_metal_ion_refined
r_metal_ion_other
r_symmetry_vdw_refined
r_symmetry_vdw_other
r_symmetry_hbond_refined
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 Atoms2986
Nucleic Acid Atoms
Solvent Atoms214
Heterogen Atoms36

Software

Software
Software NamePurpose
MOLREPphasing
REFMACrefinement
CrystalCleardata reduction
CrystalCleardata scaling