Dr. Todd Holyoak

Biography

Professor Holyoak's laboratory’s research interests lie in enzyme structure, mechanism, inhibition, and allostery. His research currently focuses on the role that conformational plasticity plays in enzymology and the dynamic aspects of enzyme structure that are exploited in the regulation of enzyme function. Holyoak is currently investigating phenomena in enzyme families including GTP-dependent phosphoenolpyruvate carboxykinases and the IgA1 protease family of bacterial proteases, using primarily tools of steady-state kinetics and X-ray crystallography. His investigations with PEPCK utilize these enzymes as a model system to understand the linkage between conformational plasticity, protein structure, and enzyme function in molecular recognition, and the implications for human health. PEPCK is an important cataplerotic enzyme activity in humans and mammals, essential for the maintenance of blood glucose levels. The flux through PEPCK contributes to fasting hyperglycemia observed in individuals afflicted with Type I and Type II diabetes and is implicated as a potential player in important biological processes such as cancer and aging. Regarding IgA1 proteases, Holyoak is interested in discovering the mechanisms of this enzyme family, which contains serine metallo-protease isoforms that selectively cleave a narrow range of protein substrates, primarily human immunoglobulin A1 (IgA1). He is particularly interested in the role that conformational flexibility plays in substrate selectivity and catalytic function of these enzymes, which are produced by several important human bacterial pathogens.

Research Interests

Courses