Catherine Drennan, Ph.D.
Department of Chemistry
Associate Professor of Chemistry
A.B. Chemistry, Vassar College, 1985
High School Science Teacher, 1985-1988
Ph.D. Biochemistry, University of Michigan, 1995
Research Fellow, University of Michigan, 1995-1996
Postdoctoral Scholar, Caltech, 1996-1999
Assistant Professor of Chemistry, MIT, 1999-2003
Associate Professor of Chemistry, MIT, 2004-present
Our laboratory uses X-ray crystallography to study the structure and mechanism of metalloproteins. The Drennan lab is located in buildings 16 and 56 and has eight graduate students, one postdoc and two to five undergraduate students. Currently, all graduate students are from the biological division of the chemistry department.
Crystallography is an invaluable tool for systems biology, proteomics, computational biology, and drug design. In the area of systems biology, the Drennan laboratory employs crystallography to understand how organisms can use pollutants, such as carbon monoxide and carbon dioxide, as sources of energy and carbon. We are studying the pathway by which acetogens convert two molecules of carbon dioxide into acetate via a series of unique metalloenzymes. By determining structures of all the enzymes in this pathway, we will be able to explore the identity of the metal cofactors, and probe the protein-protein interactions responsible for this amazing chemistry. In the area of proteomics and computational biology, we are studying a family of metalloenzymes that use radical-based chemistry to catalyze reactions ranging from vitamin and antibiotic biosynthesis to DNA repair. For the Adenosylmethionine-Radical superfamily, there are 600 unique protein sequences and one three-dimensional structure. Using bioinformatics and crystallography, we are investigating this family of proteins to ask the question, what are the structural requirements for radical-based chemistry? With respect to drug design, we are studying ribonucleotide reductases. These ezymes catalyze the rate-determining step in DNA biosynthesis and are therefore anti-tumor and anti-viral targets. Toward the long-term goal of drug design, we are using the relatively simple class II ribonucleotide reductase as a model system for crystallographic studies of enzyme complexes with substrates, inhibitors, effectors, and cofactors.
- Higgins, L. J., Yan, F., Liu P., Liu, H.-W., Drennan, C. L. (2005) "Structural Insight into Antibiotic Fosfomycin Biosynthesis by a Mononuclear Iron Enzyme," Nature 437, 838844.
- Delaney, J.C., Smeester, L., Wong, C., Frick, L. E., Taghizadeh, L., Wishnok, J. S., Drennan, C. L., Samson, L. D., Essigmann, J. M. (2005) "AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo," Nature Structural & Molecular Biology 12, 855-860.
- Berkovitch F., Behshad, E., Kuo-Hsiang Tang, K-H., Enns, E.A., Frey, P.A., and Drennan, C.L. (2004) "A Locking Mechanism Preventing Radical Damage in the Absence of Substrate, as Revealed by the X-ray Structure of Lysine 5,6-Aminomutase," Proceedings of the National Academy of Science U.S.A. 101, 1587015875.
- Berkovitch, F., Nicolet, Y., Wan, J.T., Jarrett, J.T., and Drennan, C.L. (2004) "The Crystal Structure of Biotin Synthase, an S-Adenosylmethionine-Dependent Radical Enzyme," Science 303, 76-79.
- Nicolet, Y., and Drennan, C.L. (2004) "AdoMet Radical Proteins from Structure to Evolution Alignment of Divergent Protein Sequences Reveals Strong Secondary Structure Element Conservation," Nucleic Acids Research 32, 4015-4025.
- Schreiter, E.R., Sintchak, M.D., Guo, Y., Chivers, P.T., Sauer, R.T., and Drennan, C.L., (2003) "Crystal Structure of the Nickel-Responsive Transcription Factor NikR," Nature Structural Biology 10, 794-799.
- Doukov, T.I., Iverson, T.M., Seravalli, J., Ragsdale, S.W., and Drennan, C.L. (2002) "A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase," Science 298, 567572.
- Sintchak, M.D., Arjara, G., Kellogg, B.A., Stubbe, J., and Drennan, C.L. (2002) "The Crystal Structure of Class II Ribonucleotide Reductase Reveals How an Allosterically Regulated Monomer Mimics a Dimer," Nature Structural Biology 9, 293300.
Last Updated: April 16, 2008