Using a combination of X-ray crystallography and enzymology we are studying a variety of enzymes relevant to military research. By understanding mechanisms of catalysis we can identify reversible and irreversible mechanism-based inhibitors of bacterial enzymes (potential antimicrobials). Recently, we have examined S-formylglutathione hydrolase (esterase) variants which are activated or inhibited by peroxide and may be useful as biochemical sensors or actuators. We have also determined several structures of T. californica acetylcholinesterase in complex with nerve agents and oximes. Our work has focused primarily on toxins and antimicrobial targets such as B. anthracis CapD, F. tularensis FabI, the Botulinum neurotoxin Light Chain zinc metalloprotease, and Ricin A-chain.
A second area of interest has been protein engineering to obtain thermal stabile proteins. These engineered variants retain many of the features of the native protein but have higher melting temperatures and are less prone to irreversible aggregation. Long-shelf life vaccine immunogens can reduce the costs of replenishing and maintaining strategic stockpiles. We have also determined the structure of a thermostabile antibody in collaboration with Dr. Goldman. These thermal stabile antibodies may be useful for next generation diagnostics which do not require refrigeration.