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Mentor: Amnon Kohen, PhD
Year Entered Into Program: 2005-2006
One of the primary focuses of Dr. Amnon Kohen's lab is the study of chemical catalysis in biological systems. My research focused on resolving the catalytic cascade, using pre-steady state kinetics, of flavin-dependent thymidylate synthase (FDTS) isolated from Thermotoga maritime (tmFDTS). In general, thymidylate synthase (TS) activity is essential for any living organism because it catalyzes the last committed step in the biosynthesis of thymidine. Preliminary studies have indicated that the FDTS reaction is substantially different than that of classical TS (which is found in humans). These mechanistic differences suggest that resolution of the catalytic cascade (the order of substrate binding and product release, formation of intermediate complexes, etc.) will contribute to the design and synthesis of effective inhibitors. These inhibitors will be tested in classical TS, as a measure of possible toxicity. Promising compounds will then be examined as in vitro and in vivo antibiotic drugs.
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