Evolution is the organizing principle of biology and provides the cornerstone of our approach to understand the relationships between protein structure and function. We combine bioinformatics, biochemistry, and genetics to address fundamental questions about protein evolution, such as: What structural and mechanistic features of enzymes increase their capacity to evolve new functions? How do new metabolic pathways evolve? Are there multiple evolutionary pathways to evolve new enzyme activities?
Our primary focus is on how catalytic promiscuity serves as the raw material for evolving new enzyme activities. Catalytic promiscuity is the ability to catalyze different chemical reactions using the same active site. Many enzymes in one branch of the protein family we are studying are catalytically promiscuous, and this activity has been incorporated into new metabolic pathways more than once. Comparing the sequences and structures of these proteins will identify characteristics that permitted them to evolve the second activity.
Our goal is to use results from our research to identify fundamental evolutionary principles that can can help decipher protein structure-function relationships, predict protein functions, and improve protein engineering methods.
- McMillan, A. W., Lopez, M. S., Zhu, M., Morse, B. C., Yeo, I., Amos, J., ... Glasner, M. E. (2014). Role of an Active Site Loop in the Promiscuous Activities of Amycolatopsis sp T-1-60 NSAR/OSBS. BIOCHEMISTRY. 53(27), 4434-4444.
- Odokonyero, D., Sakai, A., Patskovsky, Y., Malashkevich, V. N., Fedorov, A. A., Bonanno, J. B., ... Glasner, M. E. (2014). Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 111(23), 8535-8540.
- Odokonyero, D., Ragumani, S., Lopez, M. S., Bonanno, J. B., Ozerova, N., Woodard, D. R., ... Glasner, M. E. (2013). Divergent Evolution of Ligand Binding in the o-Succinylbenzoate Synthase Family. BIOCHEMISTRY. 52(42), 7512-7521.
- Zhu, W. W., Wang, C., Jipp, J., Ferguson, L., Lucas, S. N., Hicks, M. A., & Glasner, M. E. (2012). Residues Required for Activity in Escherichia coli o-Succinylbenzoate Synthase (OSBS) Are Not Conserved in All OSBS Enzymes. BIOCHEMISTRY. 51(31), 6171-6181.
- Pieper, U., Chiang, R., Seffernick, J. J., Brown, S. D., Glasner, M. E., Kelly, L., ... Sali, A. (2009). Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies.. Journal of Structural and Functional Genomics. 10(2), 107-125.
- McMillan, A., Odokonyero, D., Lopez, M., Woodard, D., Brizendine, A., & Glasner, M. E. (2014). Evolutionary Exploitation of Promiscuous NSAR/OSBS Enzymes. Protein Sci. 23, 252-252.
- Kalyanaraman, C., Glasner, M. E., Chiang, R., Fayazmanesh, N., Babbitt, P., & Jacobson, M. P. (2006). Ligand based clustering of alpha-beta barrel enzymes. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 232, 10-10.
- Glasner, M. E., Fayazmanesh, N., Chiang, R., Jacobson, M. P., Gerlt, J. A., & Babbitt, P. C. (2006). Evolution of structure and function in the o-succinylbenzoate synthase family. The FASEB Journal. 20(5), A905-A905.