About
Catherine Drennan seeks to understand how nature harnesses and redirects the reactivity of enzyme metallocenters in order to perform challenging reactions.
By combining X-ray crystallography and electron microscopy with other biophysical methods, a goal of the Drennan laboratory is to ‘visualize’ molecular processes by obtaining snapshots of enzymes in action. Some of the proteins studied are newly characterized, but many are well-studied but have eluded structural characterization due to issues of oxygen sensitivity, conformational flexibility or structural complexity. Drennan’s lab has specialized in tackling and solving these challenging problems in structural biology. Early in her independent career, Drennan determined one of the two first structures of carbon monoxide dehydrogenase (CODH), and the first structure of the 310-kDa bi-functional carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) enzyme complex (the latter in collaboration with Stephen Ragsdale of the University of Michigan). These long-awaited structures provided snapshots of the amazing multiple-metal centers known as the A- and C-clusters, responsible for the ability of microbes to live on carbon dioxide by converting it into acetyl-CoA in a process known as acetogenesis. These structural data prompted an upsurge in bioinorganic-model chemistry and mechanistic enzymology on this system, which is currently being pursued as an avenue for producing biofuels from carbon dioxide.
Awards
- Presidential Early Career Award for Scientists and Engineers (PECASE)
- Searle Scholar Award
- Alfred P. Sloan Fellow
Relevant Publications
Gibson, M.I., Chen, P.Y-T., Johnson, A.C.,…Drennan, C.L. (2016). One carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography. Proceedings of the National Academy of Sciences USA, 113(2), 320–25. DOI: https://doi.org/10.1073/pnas.1518537113
Kung, Y., Ando, N., Doukov, T.I.,… Drennan, C.L. (2012). Visualising Molecular Juggling within a B12-dependent Methyltransferase Complex. Nature, 484(7393), 265–69. DOI: 10.1038/nature10916.
Doukov, T.I., Iverson, T.M., Seravalli, J. Ragsdale, S.W., Drennan, C.L. (2002). A Ni-Fe- Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase. Science, 298(5593), 567-72. DOI: https://doi.org/10.1126/science.1075843
Drennan, C.L., Heo, J., Sintchak, M.D., Schreiter, E., Ludden, P.W. (2001). Life on Carbon Monoxide: X-ray Structure of Rhodospirillum rubrum Ni-Fe- S Carbon Monoxide Dehydrogenase. Proceedings of the National Academy of Sciences USA, 98(21), 11973-8. DOI: https://doi.org/10.1073/pnas.211429998
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CIFAR is a registered charitable organization supported by the governments of Canada, Alberta and Quebec, as well as foundations, individuals, corporations and Canadian and international partner organizations.