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

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

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalInternational Journal for Parasitology: Drugs and Drug Resistance
Volume13
DOIs
StatePublished - Aug 2020

Keywords

  • Drug binding
  • Oxamniquine
  • Schistosoma spp.
  • Sulfotransferase

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Pharmacology (medical)

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    Rugel, A. R., Guzman, M. A., Taylor, A. B., Chevalier, F. D., Tarpley, R. S., McHardy, S. F., Cao, X., Holloway, S. P., Anderson, T. J. C., Hart, P. J., & LoVerde, P. T. (2020). Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum? International Journal for Parasitology: Drugs and Drug Resistance, 13, 8-15. https://doi.org/10.1016/j.ijpddr.2020.04.001