Grant: Operating Grant

Our research on the structure and function of membrane proteins attacks one of the most important and challenging problems in contemporary biochemistry. Our most recent work has been focused on an outer membrane enzyme PagP from pathogenic Gram-negative bacteria. PagP transfers a palmitoyl group from a phospholipid molecule to the lipid A or endotoxin component of lipopolysaccharide. This simple modification provides bacterial resistance to host antimicrobial peptides and attenuates the inflammatory response signaled through the toll-like receptor 4 pathway. By understanding how the structural and dynamic properties of PagP relate to its biological function, we hope to design inhibitors that might be useful for the treatment of infections and to synthesize novel endotoxin analogs that function as antagonists for the treatment of septic shock or as vaccine adjuvants.