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.
Presidential Early Career Award for Scientists and Engineers (PECASE)
Searle Scholar Award
Alfred P. Sloan Fellow
Gibson, M.I. et al. “One carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography.” Proc. Natl. Acad. Sci. U.S.A. 113 (2016): 320–25.
Kung, Y. et al. “Visualising Molecular Juggling within a B12-dependent Methyltransferase Complex.” Nature 484 (2012): 265–69.
Doukov, T.I. et al. “A Ni-Fe- Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase.” Science 298 (2002).
Drennan, C.L. et al. “Life on Carbon Monoxide: X-ray Structure of Rhodospirillum rubrum Ni-Fe- S Carbon Monoxide Dehydrogenase.” Proc. Natl. Acad. Sci. U.S.A.