Matt McLeod

Matt Jordan McLeod

Asst Professor (F2)

711 Old Chemistry
Phone 5135568165

Professional Summary

The McLeod lab's research focuses on how enzyme structure and dynamics control function.  We are currently investigating 1) the three classes of phosphoenolpyruvate carboxykinase to understand how evolved modifications to the structural scaffold impart allosteric regulation and unique kinetic behaviors, 2) the temperature dependence of enzyme activity and ligand binding in a variety of enzymes, and 3) how enzymes evolve to different thermal niches (extremophiles).  

Experimental Techniques: X-ray crystallography (time-resolved, multi-temperature, high-pressure), small angle X-ray scattering, cryo-electron microscopy, enzyme kinetics, protein expression and purification, 

For more information see: www.mcleodlab.com
 

Education

Ph.D.: University of Waterloo Waterloo ON, Canada, 2020 (Structural Enzymology - Holyoak Lab)

M.Sc.: University of Waterloo Waterloo ON, Canada, 2016 (Structural Enzymology - Holyoak Lab)

B.Sc.: University of Waterloo Waterloo ON, Canada, 2014 (Honours Biomedical Sciences & Minor in Human Nutrition & Minor in Biology )

Positions and Work Experience

2020 -2025 Postdoctoral Fellow, Thorne Lab, Cornell University, Ithaca NY, USA

Publications

Peer Reviewed Publications

Indergaard, John A; Mahmood, Kashfia; Gabriel, Leo; Zhong, Gary; Lastovka, Adam; McLeod, Matthew J; Thorne, Robert E  (2025). Instrumentation and methods for efficient time-resolved X-ray crystallography of biomolecular systems with sub-10 ms time resolution. IUCrJ, 12 (Pt 3) , 372-383More Information

McLeod, Matthew J; Barwell, Sarah A E; Holyoak, Todd; Thorne, Robert E  (2025). A structural perspective on the temperature dependent activity of enzymes. Structure, 33 (5) , 924-934.e2More Information

Abdelhady, Abdallah W; Mittan-Moreau, David W; Crane, Patrick L; McLeod, Matthew J; Cheong, Soon Hon; Thorne, Robert E  (2024). Ice formation and its elimination in cryopreservation of oocytes. Scientific reports, 14 (1) , 18809More Information

Tran, Norman; Dasari, Sathish; Barwell, Sarah A E; McLeod, Matthew J; Kalyaanamoorthy, Subha; Holyoak, Todd; Ganesan, Aravindhan  (2023). The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease. Nature communications, 14 (1) , 5625More Information

McLeod, Matthew J; Holyoak, Todd  (2023). Biochemical, structural, and kinetic characterization of PPi -dependent phosphoenolpyruvate carboxykinase from Propionibacterium freudenreichii. Proteins, 91 (9) , 1261-1275More Information

Lee, Eunjeong; McLeod, Matthew J; Redzic, Jasmina S; Marcolin, Barbara; Thorne, Robert E; Agarwal, Pratul; Eisenmesser, Elan Zohar  (2023). Identifying structural and dynamic changes during the Biliverdin Reductase B catalytic cycle. Frontiers in molecular biosciences, 10, 1244587More Information

McLeod, Matthew J; Tran, Norman; McCluskey, Gregory D; Gillis, Tom D; Bearne, Stephen L; Holyoak, Todd  (2023). A metal-dependent conformational change provides a structural basis for the inhibition of CTP synthase by gemcitabine-5'-triphosphate. Protein science : a publication of the Protein Society, 32 (6) , e4648More Information

Clinger, Jonathan A; Moreau, David W; McLeod, Matthew J; Holyoak, Todd; Thorne, Robert E  (2021). Millisecond mix-and-quench crystallography (MMQX) enables time-resolved studies of PEPCK with remote data collection. IUCrJ, 8 (Pt 5) , 784-792More Information

Mcleod, Matthew J; Krismanich, Anthony P; Assoud, Abdeljalil; Dmitrienko, Gary I; Holyoak, Todd  (2019). Characterization of 3-[(Carboxymethyl)thio]picolinic Acid: A Novel Inhibitor of Phosphoenolpyruvate Carboxykinase. Biochemistry, 58 (37) , 3918-3926More Information

Cui, Danica S; Broom, Aron; Mcleod, Matthew J; Meiering, Elizabeth M; Holyoak, Todd  (2017). Asymmetric Anchoring Is Required for Efficient Ω-Loop Opening and Closing in Cytosolic Phosphoenolpyruvate Carboxykinase. Biochemistry, 56 (15) , 2106-2115More Information

Johnson, Troy A; Mcleod, Matthew J; Holyoak, Todd  (2016). Utilization of Substrate Intrinsic Binding Energy for Conformational Change and Catalytic Function in Phosphoenolpyruvate Carboxykinase. Biochemistry, 55 (3) , 575-87More Information

Balan, Marc D; Mcleod, Matthew J; Lotosky, William R; Ghaly, Mark; Holyoak, Todd  (2015). Inhibition and Allosteric Regulation of Monomeric Phosphoenolpyruvate Carboxykinase by 3-Mercaptopicolinic Acid. Biochemistry, 54 (38) , 5878-87More Information

Additional Publications

Courses Taught

-CHEM-3046L BIOCHEM LAB II

Contact Information

Academic - 711 Old Chemistry
Phone: 5135568165