4AZY

Design and Synthesis of BACE1 Inhibitors with In Vivo Brain Reduction of beta-Amyloid Peptides (COMPOUND 10)

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	1FKN	PREVIOUSLY DETERMINED BACE1 STRUCTURE BASED ON PDB ENTRY 1FKN

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1		5		11% PEG6K, 90 MM NAAC PH 5.0, 18 MM TRIS PH 8.5, 135 MM NACL

Crystal Properties
Matthews coefficient	Solvent content
2.05	40

Crystal Data

Unit Cell
Length ( ? )	Angle ( ? )
a = 47.54	�� = 90
b = 76.39	�� = 90
c = 104.34	�� = 90

Symmetry
Space Group	P 21 21 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	IMAGE PLATE	RIGAKU HTC		2008-08-20	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU FR-E

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	1.79	35.87	99.9	0.04	20.6	3.4		36601			22.03

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	1.79	1.84	100		0.26	4.5	3.4

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	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	FOURIER SYNTHESIS	THROUGHOUT	PREVIOUSLY DETERMINED BACE1 STRUCTURE BASED ON PDB ENTRY 1FKN	1.79	35.87	36544	1824	99.89	0.1775	0.1756	0.2105	RANDOM	25.06

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]
-5.5769			0.6288		4.9482

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	15.63
t_omega_torsion	4.16
t_angle_deg	1.12
t_bond_d	0.01
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	15.63
t_omega_torsion	4.16
t_angle_deg	1.12
t_bond_d	0.01
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it
t_nbd
t_improper_torsion
t_chiral_improper_torsion
t_sum_occupancies
t_utility_distance
t_utility_angle
t_utility_torsion
t_ideal_dist_contact

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2951
Nucleic Acid Atoms
Solvent Atoms	402
Heterogen Atoms	47

Software

Software
Software Name	Purpose
BUSTER	refinement
MOSFLM	data reduction
SCALA	data scaling
REFMAC	phasing

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 R01GM157729.