Abstract
S-Adenosylhomocysteine (AdoHcy) hydrolases (SAHHs) from human sources (Hs-SAHHs) bind the cofactor NAD+ more tightly than several parasitic SAHHs by around 1000-fold. This property suggests the cofactor binding site of this essential enzyme as a potential anti-parasitic drug target, e.g., against SAHH from Trypansoma cruzi (Tc-SAHH). The on-rate and off-rate constants and the equilibrium dissociation constants were determined for NAD+/NADH analogues and suggested that NADH analogues were the most promising for selective inhibition of Tc-SAHH. None significantly inhibited Hs-SAHH while S-NADH and H-NADH (Fig. 1) reduced the catalytic activity of Tc-SAHH to <10% in six minutes of exposure.
Description
This 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/10.1080/15257770903044572.
Citation
Li, Q.-S., Cai, S., Fang, J., Borchardt, R. T., Kuczera, K., Middaugh, C. R., & Schowen, R. L. (2009). Evaluation of NAD(H) analogues as selective inhibitors for Trypanosoma cruzi S-Adenosylhomocysteine hydrolase. Nucleosides, Nucleotides & Nucleic Acids, 28(5), 473–484. http://doi.org/10.1080/15257770903044572