Vivien C. Yee, PhD

Our structural biology group investigates biomedically important proteins and enzymes with interesting mechanistic questions. Some of our current projects focus on proteins involved in drug metabolism, neurodegenerative disorders, antiviral defense, or are model systems for metabolic enzymes. Our laboratory combines X-ray crystallography with modeling and mutagenesis studies to investigate several systems. One focus is on biotin-dependent enzymes which are important in a variety of metabolic processes. We study the large bacterial transcarboxylase multienzyme complex which is a model for homologous human proteins. Our structures allow us to speculate on catalytic mechanisms and the structural consequences of human disease mutations.

We are also investigating the prion protein, whose structural transformation to a pathogenic form is believed to be important in an intriguing family of neurological diseases, the spongiform encephalopathies. By comparing structures of wild-type and mutant prion proteins, our goal is to highlight structural features which may play a role in the disease process. A third project is part of a large pharmacogenomics investigation of drug metabolizing enzymes. Using a combination of experimental and computational methods, we compare wild-type and variant enzyme structures in order to understand the molecular and functional consequences of genetic polymorphisms responsible for variation in patient drug responses.