Kelly Sheppard
Assistant Professor of Chemistry

Research

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). In eukaryotes and a number of prokaryotes, Asn is directly attached to its tRNA (tRNA^Asn) by asparaginyl-tRNA synthetase (AsnRS).  Many prokaryotes do not encode AsnRS in their genomes and instead synthesize Asn on its tRNA in a two-step pathway. First an aspartyl-tRNA synthetase attaches the amino acid aspartate (Asp) to tRNA^Asn .  The Asp on the tRNA is then amidated to Asn by the amidotransferase GatCAB to form Asn-tRNA^Asn used in protein synthesis.  A number of bacteria, including known human pathogens, appear to encode both routes for making Asn-tRNA^Asn.  We are interested in determining if this is the case and if so how these organisms use both pathways.  The work will provide insight not only into the life cycles of these bacteria but also into the evolution of the Asn decoding pathways.  We are also investigating using the two-step pathway to expand the genetic code to incorporate unnatural amino acids into proteins.

Courses

CH 105 Chemical Principles I
CH 106 Chemical Principles II
CH 341 Biochemistry: Macromolecular Structure and Function w/Lab
CH 342 Biochemistry: Intermediary Metabolism

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Selected Publications

Rampias, T.#, Sheppard K.#, and Söll, D. (2010) The archaeal transamidosome for RNA-dependent glutamine biosynthesis.  Nucleic Acids Res., doi:10.1093/nar/gkq336.
# denotes authors contributed equally to this work.

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 tRNA^Gln confines the amidotransferase GatCAB to asparaginyl-tRNA^Asn 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.
# denotes authors contributed equally to this work.

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-tRNA^Asn and Glu-tRNA^Gln.  J. Biol. Chem. 282, 11866-11873.
# denotes authors contributed equally to this work.

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.
# denotes authors contributed equally to this work.

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Affiliations

American Association for the Advancement of Science
American Chemical Society
American Society of Biochemistry and Molecular Biology
American Society for Microbiology
New York Academy of Sciences

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