Structure and function of carboxypeptidase O
Proteases are involved in many aspects of normal physiology, from digestion of dietary proteins to regulation of complex intracellular signaling cascades. The metallocarboxypeptidase (CP) family of proteases is a major class of enzymes that removes single amino acids from the ends (the C-termini) of many substrates, from neuropeptides to dietary proteins. Recently a newly discovered CP, carboxypeptidase O (CPO), was found in intestinal tissues and shown to be a membrane-bound enzyme unique in its structure and substrate specificity. Many questions regarding the function of CPO remain, such as: Where is CPO found within a cell? In what tissues is CPO found within an organism? Does mutation of CPO play a role in the development of cancer? Does the unique structure of CPO suggest a unique protein folding mechanism? We have come a long way toward answering some of these questions, in parallel fashion so that multiple students can be involved in this work, but have a number of experiments remaining before we can submit the work for publication. The research proposed in this application will help to tie up loose ends on a number of these parallel, related projects.