Grant: Operating Grant

Proteins in living cells "talk" to each other for many cellular functions. One of the most common communications in all organisms is by adding (or removing) phosphate groups to proteins. As such, protein phosphorylation is a critically important regulatory mechanism. For example, addition of a phosphate group to a protein can serve to turn on (or off) the protein and triggers its biological activity. As an analogy, it would be like attaching a switch to a light bulb. Protein phosphorylation has been extensively studied in mammalian systems. By contrast, protein phosphorylation research in lower organisms such as bacteria has lagged far behind. Our laboratory was successful in determining the first structure of a bacterial tyrosine kinase - E. coli tyrosine kinase (Etk) which is involved in cell surface protection - using a technique called crystallography. This powerful technique can provide direct visualization of the three-dimensional structure of a protein. A picture is worth a thousand words! Based on the "picture", we were able to uncover important functional insights into Etk. We are also studying a unique bifunctional bacterial enzyme, serine/threonine kinase/phosphatase AceK. (Phosphatases remove phosphate groups, in contrast to kinases.) AceK enables bacterial growth in a low-glucose, high-acetate environment. It is very rare to have both phosphate addition and removal activities within a single protein; in fact, there are only two known examples. As such, Acek is an excellent target to learn how two opposing functions are accommodated in one protein, in addition to revealing biological insights. Through our research, we hope to gain a better understanding of bacterial phosphorylation. Since some of these proteins are uniquely found in bacteria, our knowledge of these key enzymes may have potential for the development of selective antibiotics in the future.