4X2U

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M1 Alanyl Aminopeptidase from P. falciparum

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	3EBG	PDB entry 3EBG

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.5	298	22% (v/v) PEG 8000, 10% (v/v) glycerol, 0.1 M Tris pH 8.5, 0.2 M MgCl2

Crystal Properties
Matthews coefficient	Solvent content
2.34	47.51

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 75.472	α = 90
b = 108.675	β = 90
c = 118.428	γ = 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	CCD	ADSC QUANTUM 315r		2014-09-01	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	AUSTRALIAN SYNCHROTRON BEAMLINE MX1	0.95370	Australian Synchrotron	MX1

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rpim I (All)	CC (Half)	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	1.5	46.59	99.6	0.098	0.027	0.999	19.4	13.3		152905			15.72

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rpim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.5	1.63	97		1.067	0.308	0.738	2.5	11.9	6101

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	Mean Isotropic B
X-RAY DIFFRACTION		FREE R-VALUE	PDB entry 3EBG	1.5	37.104	1.33	152905	7612	98.11	0.1584	0.1568	0.188	21.9

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
f_dihedral_angle_d	13.582
f_angle_d	1.639
f_chiral_restr	0.113
f_bond_d	0.016
f_plane_restr	0.009

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	7226
Nucleic Acid Atoms
Solvent Atoms	1253
Heterogen Atoms	77

Software

Software
Software Name	Purpose
Aimless	data scaling
PHENIX	refinement
PDB_EXTRACT	data extraction
PHASER	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.