4HZT

Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION	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, temperature 277K

Crystal Properties
Matthews coefficient	Solvent content
2.16	43.02

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 75.256	α = 90
b = 103.972	β = 90
c = 100.302	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+		2011-05-31	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	1.8	60	88			36789	32259	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	1.8	60	30577	1614	87.5	0.20065	0.19758	0.25636	RANDOM	28.957

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]
-0.3			-0.85		1.14

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.333
r_dihedral_angle_4_deg	15.575
r_dihedral_angle_3_deg	15.212
r_dihedral_angle_1_deg	7.951
r_scangle_it	4.968
r_scbond_it	3.171
r_mcangle_it	2.244
r_angle_refined_deg	1.937
r_mcbond_it	1.333
r_chiral_restr	0.153

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.333
r_dihedral_angle_4_deg	15.575
r_dihedral_angle_3_deg	15.212
r_dihedral_angle_1_deg	7.951
r_scangle_it	4.968
r_scbond_it	3.171
r_mcangle_it	2.244
r_angle_refined_deg	1.937
r_mcbond_it	1.333
r_chiral_restr	0.153
r_bond_refined_d	0.023
r_gen_planes_refined	0.011

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	3099
Nucleic Acid Atoms
Solvent Atoms	398
Heterogen Atoms	31

Software

Software
Software Name	Purpose
CrystalClear	data collection
MOLREP	phasing
REFMAC	refinement
d*TREK	data reduction
d*TREK	data scaling

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.