2HVX

Discovery of Potent, Orally Active, Nonpeptide Inhibitors of Human Mast Cell Chymase by Using Structure-Based Drug Design

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.5	295	30% PEG4000, 0.2 Na Acetate, 0.1 bistris propane, pH 8.5, VAPOR DIFFUSION, HANGING DROP, temperature 295K

Crystal Properties
Matthews coefficient	Solvent content
2.7	54.49

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 73.94	α = 90
b = 73.94	β = 90
c = 49.45	γ = 90

Symmetry
Space Group	P 43

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	295	IMAGE PLATE	RIGAKU RAXIS IV	osmic mirrors	2002-04-10	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU RU200	1.54

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	2.6	30	100	0.103	13.4	3.9		8431

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)
	2.6	2.69	99.9		0.352	3.8

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (All)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	2.6	30	8077	8077	793	96.5	0.245	0.245	0.229	0.274	random	29.08

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]
4.072			4.072		-8.145

RMS Deviations
Key	Refinement Restraint Deviation
c_scangle_it	2.654
c_mcangle_it	2.006
c_scbond_it	1.752
c_angle_deg	1.563
c_mcbond_it	1.175
c_bond_d	0.008

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1755
Nucleic Acid Atoms
Solvent Atoms	107
Heterogen Atoms	28

Software

Software
Software Name	Purpose
CNS	refinement
PDB_EXTRACT	data extraction
DENZO	data reduction
SCALEPACK	data scaling
CNS	phasing

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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.