Cai, SuminLi, Qing-ShanFang, JianwenBorchardt, Ronald T.Kuczera, KrzysztofMiddaugh, C. RussellSchowen, Richard L.2017-06-272017-06-272009-05Cai, S., Li, Q.-S., Fang, J., Borchardt, R. T., Kuczera, K., Middaugh, C. R., & Schowen, R. L. (2009). The Rationale for Targeting the NAD/NADH Cofactor Binding Site of Parasitic S-Adenosyl-L-homocysteine Hydrolase for the Design of Anti-parasitic Drugs. Nucleosides, Nucleotides & Nucleic Acids, 28(5), 485–503. http://doi.org/10.1080/15257770903051031https://hdl.handle.net/1808/24659This is an Accepted Manuscript of an article published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids in May 2009, available online: http://www.tandfonline.com/10.1080/15257770903051031.Trypanosomal S-adenoyl-L-homocysteine hydrolase (Tc-SAHH), considered as a target for treatment of Chagas disease, has the same catalytic mechanism as human SAHH (Hs-SAHH) and both enzymes have very similar X-ray structures. Efforts toward the design of selective inhibitors against Tc-SAHH targeting the substrate binding site have not to date shown any significant promise. Systematic kinetic and thermodynamic studies on association and dissociation of cofactor NAD/H for Tc-SAHH and Hs-SAHH provide a rationale for the design of anti-parasitic drugs directed toward cofactor-binding sites. Analogues of NAD and their reduced forms show significant selective inactivation of Tc-SAHH, confirming that this design approach is rational.Article10.1080/15257770903051031PMC4128003openAccess