SSRL scientists have determined key binding sites in an enzyme family common to Anthrax, Botulism, Syphilis, Diarrhea and Lyme's disease. The protein x-ray crystallography data have already enabled the scientists to create a computer model of a molecule that could inhibit the enzyme's activity, which is essential for many single-celled organisms to replicate. The unique structure of the enzyme - thymidylate synthase complementing protein (TSCP) - and the recent discovery of TSCP in numerous pathogenic organisms provide an exciting opportunity for drug design. TSCP catalyzes the building of dTMP, the structure that contains "T", one of the four letters in the DNA alphabet. Cells need all four letters - A, C, G, and T - to copy themselves. TSCP is an especially attractive target for therapeutic intervention because the enzyme that performs the same task in humans is completely different, which reduces the chances of interfering with necessary cell activity in people being treated. Research efforts centered at SSRL have elucidated the structural and functional relationship of TSCP in a high-temperature bacterium, and mapped out many of the principal binding configurations. The studies have also revealed novel features of the TSCP enzyme family. For example, a multipurpose molecule called FAD binds to TSCP differently than it does to other enzymes, making it a good spot to stop TSCP without affecting other cellular functions that use FAD in humans. A proposed design for a TSCP inhibitor has been derived from detailed analysis of the structural data [Structure, 11, 677 (2003); Editorial review: ibid, 607]. The development of specific and selective TSCP inhibitors could supply highly effective tools for therapeutic intervention with low cross reactivity against the mammalian counterpart enzyme, called thymidylate synthase (TS). This work was carried out in association with the NIH funded Joint Center for Structural Genomics (JCSG) whose structure determination core is located at SSRL.