Department of Chemistry
Krieger School of Arts & Sciences
B.S. 1979, University of California, Berkeley
Ph.D. 1983, Massachusetts Institute of Technology
124 Remsen Hall
3400 N. Charles Street
Baltimore, MD 21218
Our research program is united by a common interest in describing the structure and activity of biological macromolecules through their essential chemical reactivity. The methods of biophysics, biochemistry and organic chemistry are applied to questions on enzyme catalysis and nucleic acid modification. Current projects include enzymatic dehalogenation and reversible covalent chemistry expressed by quinone methide intermediates.
Organohalides are distributed widely in the environment and originate from both biological and industrial sources. Under aerobic conditions, these compounds are typically consumed by oxidative and hydrolytic metabolism. However, animals also express the unusual ability to promote reductive dehalogenation of natural iodotyrosine derivatives related to the thyroid hormone thyroxine. Iodide recovery from these compounds is promoted by iodotyrosine deiodinase, an enzyme crucial for human health. Investigations are currently designed to understand the mechanism of this enzyme and the role of its bound flavin in catalysis. Flavin-dependent reactions are associated with a wide variety of metabolic transformations but its use in reductive dehalogenation is quite rare. Results of this research will help to expand the known repertoire of flavin chemistry and will guide its future use in bioremediation of organohalide pollutants.
Buss, J.M., P.M. McTamney, and S.E. Rokita. (2012) Expression of a soluble form of iodotyrosine deiodinase for active site characterization by engineering the native membrane protein from Mus musculus. Protein Sci. 21:351-361.
Liu, Y., and S.E. Rokita (2012) Inducible alkylation of DNA by a quinone methide-peptide nucleic acid conjugate. Biochemistry 51:1020-1027.
McCrane, M.P., E.E. Weinert, Lin, Y., Mazzola, E.P., Lam, Y-F., Scholl, P.F., and S.E. Rokita. (2011) Trapping a labile adduct formed between an ortho-quinone methide and 2'-deoxycytidine. Org. Lett. 13:1186-1189.
Fakhari, M.A., and S.E. Rokita. (2011) A new solvatochromic fluorophore with high sensitivity for studying biopolymers. Chem. Commun. 47:4222-4224.
Rokita, S.E., J.M. Adler, P.M. McTamney, and J.A. Watson, Jr. (2010) Efficient use and recycling of the micronutrient iodide in mammals. Biochimie 92:1227-1235.
Rossiter, C.S., E. Modica, D. Kumar, and S.E. Rokita. (2011) Few constraints limit the design of quinone methide-oligonucleotide self-adducts for directing DNA alkylation. Chem. Commun. 47:1476-1478.
Wang, H., and S.E. Rokita. (2010) Dynamic cross-linking is retained in duplex DNA after multiple exchange of strands. Angew. Chem. Int. Ed. 49:5957-5960.
Thomas, S.R., P.M. McTamney, J.M. Adler, N. LaRonde-LeBlanc, and S.E. Rokita. (2009) Crystal structure of iodotyrosine deiodinase, a novel flavoprotein responsible for iodide salvage in thyroid glands. J. Biol. Chem. 284:19659-19667.
McTamney, P.M., and S.E. Rokita. (2008) A mammalian reductive deiodinase has broad power to dehalogenate chlorinated and brominated substrates. J. Am. Chem. Soc. 131:14212–14213.