2VIV

Fragment-Based Discovery of Mexiletine Derivatives as Orally Bioavailable Inhibitors of Urokinase-Type Plasminogen Activator

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1		6.6		PROTEIN WAS CRYSTALLIZED FROM 22-24% PEG4000, 0.17M (NH4)2SO4, 15% GLYCEROL, 0.1M NA(CH3COO) PH=4.0; THEN SOAKED IN 0.04M COMPOUND, 28% PEG4000, 5% GLYCEROL, 0.29M BISTRIS PH=6.6, 0.001M NA(CH3COO), 0.001M (NH4)2SO4

Crystal Properties
Matthews coefficient	Solvent content
1.86	39.54

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 52.338	α = 90
b = 54.001	β = 90
c = 81.938	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	93	CCD	RIGAKU CCD	OSMIC BLUE CONFOCAL OPTICS		M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU RUH3R

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	1.72	34.16	82.8	0.06		2.4		21002

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	1.72	1.73	22.6		0.29	2

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	OTHER	THROUGHOUT	NONE	1.72	34.16	21002	1044	82.75	0.183	0.1801	0.2377	RANDOM

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]

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1952
Nucleic Acid Atoms
Solvent Atoms	224
Heterogen Atoms	32

Software

Software
Software Name	Purpose
BUSTER-TNT	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 R01GM157729.