Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum?

Rugel, Anastasia R.; Guzman, Meghan A.; Taylor, Alexander B.; Chevalier, Frédéric D.; Tarpley, Reid S.; McHardy, Stanton F.; Cao, Xiaohang; Holloway, Stephen P.; Anderson, Timothy J. C.; Hart, P. John; LoVerde, Philip T.

doi:10.1016/j.ijpddr.2020.04.001

Title: Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum?

Journal Article · Sat Aug 01 00:00:00 EDT 2020 · International Journal for Parasitology, Drugs and Drug Resistance

DOI:https://doi.org/10.1016/j.ijpddr.2020.04.001· OSTI ID:1771833

Rugel, Anastasia R.; Guzman, Meghan A.; Taylor, Alexander B.; Chevalier, Frédéric D.; Tarpley, Reid S.; McHardy, Stanton F.; Cao, Xiaohang; Holloway, Stephen P.; Anderson, Timothy J. C.; Hart, P. John; LoVerde, Philip T.

Human schistosomiasis is a disease which globally affects over 229 million people. Three major species affecting humans are Schistosoma mansoni, S. haematobium and S. japonicum. Previous treatment of S. mansoni includes the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The OXA activating enzyme was identified and crystallized, as being a S. mansoni sulfotransferase (SmSULT). S. haematobium and S. japonicum possess homologs of SmSULT (ShSULT and SjSULT) begging the question; why does oxamniquine fail to kill S. haematobium and S. japonicum adult worms? Investigation of the molecular structures of the sulfotransferases indicates that structural differences, specifically in OXA contact residues, do not abrogate OXA binding in the active sites as previously hypothesized. Data presented argue that the ability of SULTs to sulfate and thus activate OXA and its derivatives is linked to the ability of OXA to fit in the binding pocket to allow the transfer of a sulfur group.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID); Welch Foundation

Grant/Contract Number:: AC02-06CH11357; R01 AI115691; AQ-1399; HHSN272201000005I; NIH P30 CA054174; P41 GM103403; S10 RR029205

OSTI ID:: 1771833

Alternate ID(s):: OSTI ID: 1617500

Journal Information:: International Journal for Parasitology, Drugs and Drug Resistance, Journal Name: International Journal for Parasitology, Drugs and Drug Resistance Vol. 13 Journal Issue: C; ISSN 2211-3207

Publisher:: ElsevierCopyright Statement

Country of Publication:: Netherlands

Language:: English

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Cited by: 7 works

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