The search for developing new antibiotics is a battle against evolution that hinges on a few basic criteria. For one, the antibiotic must target a cellular process that is vital for growth of the bacterium so that it may not be bypassed by another set of metabolic reactions. The target also needs to be specific to pathogens. NAD Kinase is an ideal antibiotic target because current literature suggests that it is essential for life due to the key role it plays in the NAD(H)/NADP(H) balance within the cell. Furthermore, kinetic studies conducted in this lab have identified two molecules that selectively inhibit the Salmonella enterica NAD kinase (S. NADK) over the human variant of the enzyme. We set out to cocrystallize S. NADK with each of these inhibitors in order to locate their respective binding sites and elucidate their mechanisms of action. Unfortunately, analysis of X-ray crystallography data collected has not indicated the presence of any bound ligands, yet efforts are still under way to obtain a ligand-bound structure. However, progress has been made in identifying crystallization conditions which consistently produce apoenzyme crystals, and evidence suggests that an NADK antibiotic scaffold may be effective across multiple prokaryotic species.

Structural studies of Salmonella enterica NAD kinase: An investigation of a novel antibiotic target

251st National Meeting (2016)

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