Silver Bullets screens a portfolio of small molecules for their ability to establish stabilizing, inter molecular, hydrogen bonding, hydrophobic and electrostatic interactions which could promote stability, lattice formation, and crystallization.1-3
Published results with the Silver Bullets have been very encouraging, with more than twice as many proteins being crystallized overall as were crystallized from controls free of any small molecules.1-3
X-ray diffraction analysis has revealed the small molecule Silver Bullets in the crystal lattice, involved at the centers of hydrogen bonding networks and electrostatic interaction.1-3 Silver Bullets is compatible with hanging, sitting and sandwich drop vapor diffusion, microbatch, free interface, and microdialysis crystallization methods. Silver Bullets can be used with Dynamic Light Scattering (DLS), ThermoFluor, and Size Exclusion Chromatography assays.
Silver Bullets reagent portfolio
•Organic salts and acids
•Biologically active small molecules
•Amino acids and peptides
The Silver Bullets kit is a library of small molecules that have been shown to promote crystal lattice formation. X-ray diffraction analysis has demonstrated the reagents have the ability to:
•Stabilize the conformation of the protein
•Perturb the interaction of the protein with the solvent
•Participate in forming important lattice contacts
•Build the crystal lattice by forming reversible cross-links between the macromolecules in the crystal
The Silver Bullets kit is composed of 96 solutions in a single Deep Well block (Greiner 786261 block specifications: Total Volume: 0.5 mL Working Volume: 0.03 - 0.7 mL at Room Temperature 0.03 - 0.55 mL at -20ďż˝C, Well Profile: Conical (V), Bottom Well Bottom: Solid, Plate Color: Translucent), HT format.
Each Silver Bullets reagent is a mixture of small molecules or macromolecular digests in 0.02 M HEPES sodium pH 6.8 buffer. Each solution contains between 2 and 20 small molecules.
Silver Bullets reagent volume is 0.5 ml (each well).
ThermoFluor is a registered trademark of Johnson & Johnson.
1. Searching for silver bullets: An alternative strategy for crystallizing macromolecules. Alexander McPherson and Bob Cudney. Journal of Structural Biology 156 (2006) 387-406.
2. A novel strategy for the crystallization of proteins: X-ray diffraction validation. Steven B. Larson, John S. Day, Robert Cudney, and Alexander McPherson. Acta Cryst. (2007) D63, 310-318.
3. Development of an alternative approach to protein crystallization. Alexander McPherson, Chieniang Nguyen, Steven B. Larson, John S. Day and Bob Cudney. Journal of Structural and Functional Genomics, DOI 10.1007/s10969-007-9034-3, November 2007
4. Development of an alternative approach to protein crystallization. McPherson, Alexander; Nguyen, Chieniang; Larson, Steven B; Day, John S; Cudney, Bob. J Struct Funct Genomics, Volume 8, Number 4, December 2007, 193-198.
5. Progress in the Development of an Alternative Approach to Macromolecular Crystallization. S. B. Larson,J. S. Day, C. Nguyen, R. Cudney, and A. McPherson. Crystal Growth & Design 2008 Volume 8, No. 8 3038-3052.
6. High-resolution structure of proteinase K cocrystallized with digalacturonic acid. S. B. Larson, J. S. Day, C. Nguyen, R. Cudney and A. McPherson. Acta Cryst. (2009). F65, 192-198.
7. Structure of pig heart citrate synthase at 1.78 Angstrom resolution. Steven B. Larson, John S. Day, Chieugiang Nguyen, Robert Cudney and Alexander McPherson. Acta Cryst. (2009). F65, 430-434.
8. Crystallization and preliminary X-ray diffraction analysis of the dimerization domain of the tumour suppressor ING4. Simone Culurgioni et al, Acta Cryst. (2010). F66, 567-570.