Todd Holyoak

Dr. Todd Holyoak is an Associate Professor in the Department of Biology whose research interests lie in the areas of enzyme structure, mechanism, inhibition and allostery.

Holyoak’s research studies the role that conformational plasticity plays in these areas of enzymology and how these dynamic aspects of enzyme structure can be exploited in the regulation of enzyme function. The Holyoak lab is currently investigating these phenomena in various enzyme families with a current focus on the origins of selectivity in bacterial immunoglobulin proteases using various biophysical the tools such as well as structural approaches such as Xray crystallography and Xray scattering.

Bacteria that produce these immunoglobulin hydrolyzing enzymes are important human pathogens, and as such, generating a mechanistic understanding of how these enzymes function can be used to develop new antibacterial and antiviral therapeutics. Additional classes of immunoglobulin proteases are also produced by key members of the human gut microbiome Examination of the proteases produced by these human gut inhabiting organisms will give us a better understanding of the origins of inflammatory diseases such as colitis, Crohn’s disease and gluten intolerance. Both classes of enzymes have the opportunity to be re-engineered into therapeutic agents themselvs to treat human autoimmune as well as diseases associated with abbaraent immunoglobuilins deposition such as IgA nephropathy. In these various ways, his research aims to improve human health.

• Enzymology

• Structural biology macromolecular crystallography

• Recombinant protein expression

• Drug discovery, design and delivery

• Biochemistry and biophysics

• Microbiology

• Bioinformatics, systematics and evolution

• 2000, PhD Biochemistry, University of Notre Dame, United States

• 1994, BSc Biochemistry, University of Waterloo, Canada

• American Crystallographic Association

• The Protein Society

• American Chemical Society

• Waterloo Centre for Microbial Research (Member)

• Waterloo Institute for Nanotechnology (Member)

• BIOL 130 - Introductory Cell Biology
  • Taught in 2022, 2023
• BIOL 465 - Structural Bioinformatics
  • Taught in 2022, 2023, 2025, 2026

* Only courses taught in the past 5 years are displayed.

• For the full list of Todd Holyoak's publications, please see ORCID or Research Gate.

• McLeod, M.J., Barwell, S., Holyoak, T., and Thorne, R.E. (2025). A structural perspective on the temperature-dependent activity of enzymes. Structure. 3, 924-934 https://doi.org/10.1016/j.str.2025.02.013

• Tran, N., Frenette, A., and Holyoak, T. (2025). Structure of the Thomasclavelia ramosa immunoglobulin A protease reveals a modular and minimizable architecture distinct from other immunoglobulin A proteases. Proc. Nat. Acad. Sci. 122,e2503549122 https://doi.org/10.1073/pnas.2503549122

• Tran, N., Dasari, S., Barwell, S., McLeod, M., Kalyaanamoorthy, S., Holyoak, T#., and Ganesan, A#.#co-corresponding authors. (2023). The H163A Mutation Unravels an Oxidized Conformation of the SARSCoV-2 Main Protease. Nat. Comm. 14:5625 https://doi.org/10.1038/s41467-023-40023-4

• McLeod MJ, Yazdani S, Barwell SAE, Holyoak T. (2025). Structural mechanisms for cold-adapted activity of phosphoenolpyruvate carboxykinase. Protein Science. 2025;34(11):e70326. https://doi.org/10.1002/pro.70326

• Sullivan, S.M. and Holyoak, T. (2008). Enzymes with lid-gated active sites must operate by an induced fit mechanism instead of conformational selection. Proc Natl Acad Sci USA 2008;105:13829-13834. https://doi.org/10.1073/pnas.0805364105

• Ganesan, A., Holyoak, T., Kalyaanamoorthy, S., Tran, N., 2022. Methods and Proteins for Targeting Main Protease of Coronavirus. U.S. Provisional Patent Application No. 63/425,496, filed November 15, 2022

• Holyoak, T., Tran, N., Frenette, A., 2022. IgA Protease Polypeptide Agents. U.S. Provisional Patent Application No. 63/424,585, filed November 11, 2022

• Holyoak, T., Plaut, A.G., Qui, J. IgA1 Protease Polypeptide Agents and Uses Thereof.

• Holyoak, T., Carlson, G., Sullivan, S., Stiffin, R., Inhibitor Scaffold for the Inhibition of the Enzyme Phosphoenolpyruvate Carboxykinase.