Department Chair and Associate Professor of Chemistry
Office: Dana 274
At Skidmore since 2010
A.B. 1999, Occidental College
Ph.D. 2007, Yale University
Postdoctoral Associate, 2007-2010, Yale University
My research group is interested in the different pathways organisms use to translate the genetic code, in particular with regard to the amino acid asparagine (Asn). To translate Asn codons requires forming the adapter molecule asparaginyl-transfer RNA (Asn-tRNA), a step essential for all of life. In nature, two distinct routes have evolved to form this vital adapter molecule.
A number of bacteria, including known human pathogens, appear to encode both routes. Informed by advances in biochemistry, molecular genetics, microbiology, and molecular evolution, we are interested in determining if this is the case and if so how these organisms use both pathways.
The work provides insight not only into the life cycles of these bacteria but also into the evolution of the Asn decoding pathways. The research also lays the foundation for development of new antibiotics to target these pathogenic bacteria. We are also applying our knowledge of these pathways to expand the genetic code to incorporate unnatural amino acids into proteins to facilitate studies on Alzheimer’s Disease and more active anti-cancer agents.
Student collaborators gain expertise in molecular subcloning, PCR, protein overproduction and purification, plasmid mini/maxi-preparations, E. coli complementation studies, chromatography, gel electrophoresis, enzyme kinetics, buffer and reagent preparation, sequence analysis, and in vitro transcription as well as learn how to handle DNA, RNA, and proteins appropriately.
The work has been supported by grants from the National Science Foundation and Research Corporation. Students have the opportunity to present their research at regional, national, and international meetings as well as publish in peer-reviewed journals.
- CH 125 Chemical Principles (lecture and lab)
- CH 341 Biochemistry: Macromolecular Structure & Function
- CH 342 Biochemistry: Intermediary Metabolism
- CH 343 Experimental Biochemistry Laboratory
- CH 377/378 Senior Seminar in Chemistry and Biochemistry
- SSP 100 Scribner Seminar-Coming of Age:Food, Drugs and Sex after the Biotech Revolution
Selected Publications (*authors contributed equally to this work; Skidmore Undergraduates are underlined)
- Nair, N., Raff, H., Islam, M.T., Feen, M., Garofalo, D.M., and Sheppard, K. (2016) The Bacillus subtilis and Bacillus halodurans aspartyl-tRNA synthetases retain recognition of tRNAAsn. J. Mol. Biol. 428, 618-630.
- Suzuki, T., Nakamura, A., Kato, K., Söll, D., Tanaka, I., Sheppard, K., and Yao, M. (2015) Structure of the Pseudomonas aeruginosa transamidosome reveals unique aspects of bacterial tRNA-dependent asparagine biosynthesis. Proceedings of the National Academy of Sciences 112, 382-387.
- Alperstein, A., Ulrich, B., Garofalo, D.M., Dreisbach, R., Raff, H., and Sheppard, K. (2014) The predatory bacterium Bdellovibrio bacteriovorus aspartyl-tRNA synthetase recognizes tRNAAsn as a substrate. PLoS ONE 9(10): e110842.
- Mladenova, S.R., Stein, K.R., Bartlett, L., and Sheppard, K. (2014) Relaxed tRNA specificity of the Staphylococcus aureus aspartyl-tRNA synthetase enables RNA-dependent asparagine biosynthesis. FEBS Lett. 588, 1808-1812.
- O'Donoghue, P., Sheppard, K., Nureki, O., and Söll, D. (2011) Rational design of an evolutionary precursor of glutaminyl-tRNA synthetase. Proc. Natl. Acad. Sci. U.S.A. 108, 20485-20490.
- Englert, M., Sheppard, K., Aslanian, A., Yates III, J., and Söll, D. (2011) Archaeal 3'-phosphate RNA splicing ligase characterization identifies the missing component in tRNA maturation. Proc. Natl. Acad. Sci. U.S.A. 108, 1290-1295.
- Englert, M., Sheppard, K., Gundllapalli, S., Beier, H., and Söll, D. (2010) Branchiostoma floridae has separate healing and sealing enzymes for 5'-phosphate RNA ligation. Proc. Natl. Acad. Sci. U.S.A. 107, 16834-16839.
- Rampias, T.*, Sheppard K.*, and Söll, D. (2010) The archaeal transamidosome for RNA-dependent glutamine biosynthesis. Nucleic Acids Res. 38, 5774-5783.
- Wu, J., Bu, W., Sheppard, K., Kitabatake, M., Kwon, S-T., Söll, D., and Smith, J.L. (2009) Insights into tRNA-dependent amidotransferase evolution and catalysis from the structure of the Aquifex aeolicus enzyme. J. Mol. Biol. 391, 703-716.
- Sheppard, K., Sherrer, R.L., and Söll, D. (2008) Methanothermobacter thermautotrophicus tRNAGln confines the amidotransferase GatCAB to asparaginyl-tRNAAsn formation. J. Mol. Biol. 377, 845-853.
- Sheppard, K., and Söll, D. (2008) On the evolution of the tRNA-dependent amidotransferases, GatCAB and GatDE. J. Mol. Biol. 377, 831-844.
- Sheppard, K.*, Yuan, J.*, Hohn, M.J., Jester, B., Devine, K., and Söll, D. (2008) From one amino acid to another: tRNA-dependent amino acid biosynthesis. Nucleic Acids Res. 36, 1813-1825.
- Sheppard, K., Akochy, P.M., and Söll, D. (2008) Assays for transfer RNA-dependent amino acid biosynthesis. Methods 44, 139-145.
- Sheppard, K.*, Akochy, P.M.*, Salazar, J.C., and Söll, D. (2007) The Helicobacter pylori amidotransferase GatCAB is equally efficient in glutamine-dependent transamidation of Asp-tRNAAsn and Glu-tRNAGln. J. Biol. Chem. 282, 11866-11873.
- Oshikane, H.*, Sheppard, K.*, Fukai, S., Nakamura, Y., Ishitani, R., Numata, T., Sherrer, R.L., Feng, L., Schmitt, E., Panvert, M., Blanquet, S., Mechulam, Y., Söll, D., and Nureki, O. (2006) Structural basis of RNA-dependent recruitment of glutamine to the genetic code. Science 312, 1950-1954.
American Association for the Advancement of Science
American Chemical Society
American Society for Biochemistry and Molecular Biology
American Society for Microbiology
Council on Undergraduate Research
New York Academy of Sciences