3VFE

Virtual Screening and X-Ray Crystallography for Human Kallikrein 6 Inhibitors with an Amidinothiophene P1 Group

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	hanging drop	8.5	291	0.20 M trimethylamine N-oxide, 0.1 M Tris-HCl pH8.5, 20% PEG MME 2000 and 10 mM benzamidine, hanging drop, temperature 291K

Crystal Properties
Matthews coefficient	Solvent content
2.32	46.94

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 43.938	α = 90
b = 47.909	β = 90
c = 107.553	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 4		2007-05-20	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ESRF BEAMLINE ID23-1	0.933	ESRF	ID23-1

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	1.88	40	97.9	0.058	9.8	2.9		18779

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	1.88	1.95	97.2		0.268		2.8	1814

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Number Reflections (All)	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	PDB ENTRY 1LO6	1.88	28.71	18739	17947	755	93.6	0.195	0.193	0.223	RANDOM	21.5063

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]
6.73			-4.72		-2.01

RMS Deviations
Key	Refinement Restraint Deviation
c_dihedral_angle_d	21.7
c_scangle_it	3.17
c_scbond_it	2.12
c_mcangle_it	1.86
c_angle_deg	1.3
c_mcbond_it	1.2
c_improper_angle_d	1.17
c_bond_d	0.004

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1699
Nucleic Acid Atoms
Solvent Atoms	154
Heterogen Atoms	37

Software

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

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.