Dr. Martin St. Maurice has received a 3 year grant from NIH to study and biochemically characterize a fungal enzyme that may be a key therapeutic target in protecting immunocompromised patients from systemic yeast infections. Candida albicans is a ubiquitous yeast with which all of us are in regular contact. It is responsible for superficial and easily treated infections such as oral thrush or vaginitis. However, Candida infections can occasionally spread through the body and become life threatening. This is a particular concern for patients with weakened immune systems, such as late stage AIDS patients, patients undergoing chemotherapy, and organ transplant recipients. Dr. St. Maurice’s lab is researching an enzyme called urea amidolyase that is unique to just a few fungal species, including Candida. Research from other groups has shown that this enzyme is required for Candida to escape basic immune defenses and spread through the host. By better characterizing the structure and function of this enzyme, they hope to contribute to the development of therapeutic agents that will help immunocompromised patients fight systemic Candida infections.
Urea amidolyase is a complex enzyme, with many components and moving parts. The St. Maurice lab’s approach is to characterize the structure of the individual components by X-ray crystallography and, ultimately, to determine the structure of the entire enzyme. They have determined the first structure of this enzyme’s amidase domain, revealing many new insights into how this component of the enzyme functions. Their next challenge is to begin connecting the structures of the enzyme’s individual components into a more complete picture of how the enzyme functions as a whole. The lab uses X-ray crystallography, enzyme kinetics, and yeast genetics to better characterize this complicated and important human health target.