The major findings in our work on viral enzymes are associated with discovering how the proteinases and the polymerases work. With this critical knowledge, the design of more effective inhibitors that can be developed into antiviral compounds will be assisted. For example, our work with ViroChem Pharma Inc. has led to several compounds to treat HCVthat are in clinical trials.
Lysine biosynthesis takes place in plants and bacteria. Humans depend upon their diet for lysine. Our work on the DAP aminotransferase could be used to increase the yield of lysine in plants making them more nutritious for our diets. Inhibitors of this enzyme could be developed into herbicides that would be used to eradicate those plants deemed to be weeds. This same enzyme is also found in various species of Chlamidia. Clearly, the development of an inhibitor of the DAP aminotransferase of Chlamidia would be a major discovery in the effort to eradicate this insidious STD.
We have made three major discoveries in the field of antibiotic development against tuberculosis. Firstly, we have a potential inhibitor of ornithine transcarbamylase. Secondly, we have discovered two inhibitors of an epoxide hydrolase from Mtb. These inhibitors have Ki's of ~10 nM. We have determined the structure of EHB bound to one of these inhibitors; it contributes to our understanding of the catalytic mechanism of the epoxide hydrolases and will contribute greatly in the development of better inhibitors.
The structure of the arginine co-repressor, Rv1657, bound to a 16 base-pair segment of DNA with the operator sequence, has the prospect of enhancing the tightness of binding to the operator DNA. This will contribute to shutting down the biosynthetic pathway for arginine and, hopefully, to killing the bacterium.