Schistosoma mansoni sulfotransferase (SmSULT-OR) (SmSULT-OR)

Schistosoma mansoni sulfotransferase (SmSULT-OR) is a cytosolic enzyme produced by the parasitic flatworm Schistosoma mansoni that is essential for the efficacy of the anthelmintic drug oxamniquine (Valentim et al., 2013). The enzyme functions by transferring a sulfate group from the donor molecule 3-phosphoadenosine-5-phosphosulfate (PAPS) to the primary alcohol group of oxamniquine (Taylor et al., 2013). This sulfonation converts the prodrug into a highly unstable sulfate ester, which spontaneously dissociates to form a reactive electrophilic carbocation (Paveley et al., 2015). This reactive intermediate then covalently binds to the parasite DNA, causing irreversible damage and leading to the death of the worm (Valentim et al., 2013). Because SmSULT-OR is the sole activator of oxamniquine, it serves as a critical determinant of drug sensitivity. Consequently, genetic mutations or deletions in the SmSULT-OR gene are the primary mechanism of drug resistance in schistosome populations (Chevalier et al., 2014). The enzyme specific activity in S. mansoni also explains the lack of oxamniquine efficacy against other species like S. haematobium, which possess non-functional orthologs (Valentim et al., 2013).

Other names

Oxamniquine-activating sulfotransferaseSmSULTSmp_089320Sulfotransferase SmSULT-OR

SmSULT-OR activates the prodrug oxamniquine by catalyzing its sulfonation; the resulting reactive sulfate ester dissociates into a carbocation that alkylates parasite DNA, leading to worm death (Valentim et al., 2013; Taylor et al., 2013).