Professor of Biology and Chemistry Investigator and Professor , Howard Hughes Medical Institute MacVicar Faculty Fellow
CATHERINE L. DRENNAN is a professor of Biology and Chemistry at the Massachusetts Institute of Technology, and a professor and investigator with the Howard Hughes Medical Institute. By combining X-ray crystallography and electron microscopy with other biophysical methods, the Drennan laboratory goal is to “visualize” molecular processes by obtaining snapshots of enzymes in action.
The Drennan laboratory seeks to understand how nature harnesses and redirects the reactivity of enzyme metallocenters to perform challenging reactions. By combining X-ray crystallography with other biophysical methods, their goal is to "visualize" molecular processes by obtaining snapshots of enzymes in action. Why Snapshots? Suppose you want to understand the process by which a mechanic changes the battery in your car. One photo of a mechanic standing by the car won't do the trick, but a series of photos of the mechanic changing the battery would be informative. The same is true when you want to understand a cellular process; one image of a key enzyme tells you only so much. Thus, the Drennan laboratory uses multiple biophysical methods to aid in the "visualization" of complex enzyme processes. Which Enzymes? The Drennan lab wants to understand how nature performs the most challenging chemical reactions. Often, these reactions require the use of organic cofactors or metal ions, which enhance enzyme reactivity. Thus, metallo- and cofactor-dependent enzymes are our primary targets. For example, the reaction of class I ribonucleotide reductase (RNR) utilizes a di-iron cofactor to generate protein-based radical species, essential for the reduction of ribonucleotides to deoxyribonucleotides. Although enzymes like RNR are important and fascinating to study using structural methods, their structural characterization is often non-trivial due to issues such as conformational flexibility, protein heterogeneity, structural complexity, and oxygen sensitivity. The Drennan laboratory has specialized in tackling and solving these challenging structural biology problems. In addition to the focus on radical-based enzymology, the Drennan lab also studies metallo- and cofactor-containing enzymes involved in carbon dioxide sequestration and methylation chemistry. They are also broadly interested in how metallocofactors are assembled on their target enzyme. Although the main technique of the Drennan lab is X-ray crystallography, their toolbox also includes small-angle X-ray scattering and cryo-electron microscopy. By combining techniques, the Drennan lab strives to unmask the secrets of metalloenzyme reactivity: from unveiling the three-dimensional structures of newly discovered metallocenters to "watching" these enzymes juggle and communicate as they carry out their chemical reactions.