4LVA

Fragment-based Identification of Amides Derived From trans-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.6	292	0.2uL + 0.2uL drops containing 6mg/mL Nampt, 0.1M Sodium phosphate, 25-29% polyethylene glycol 3350, 0.2M NaCl, 1mM compound, pH 8.6, VAPOR DIFFUSION, HANGING DROP, temperature 292K

Crystal Properties
Matthews coefficient	Solvent content
2.34	47.45

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 60.511	α = 90
b = 106.799	β = 96.59
c = 83.04	γ = 90

Symmetry
Space Group	P 1 21 1

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	RAYONIX MX-300		2012-08-30	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	CLSI BEAMLINE 08ID-1	0.97949	CLSI	08ID-1

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (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	1.55	50	100			151480	151480	2	2

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.55	1.61	100

Refinement

Statistics
Diffraction ID	Structure Solution Method	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	1.55	46.37	1.35	151480	151425	7612	99.92	0.178	0.1765	0.2069

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	13.739
f_angle_d	1.596
f_chiral_restr	0.106
f_bond_d	0.015
f_plane_restr	0.009

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	7519
Nucleic Acid Atoms
Solvent Atoms	1006
Heterogen Atoms	146

Software

Software
Software Name	Purpose
HKL-2000	data collection
PHASER	phasing
PHENIX	refinement
DENZO	data reduction
SCALEPACK	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.