Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum?
| العنوان: | Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum? |
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| المؤلفون: | Reid S. Tarpley, Philip T. LoVerde, P. John Hart, Tim J. Anderson, Stanton F. McHardy, Stephen P. Holloway, Anastasia R. Rugel, Meghan A. Guzman, Xiaohang Cao, Frédéric D. Chevalier, Alexander B. Taylor |
| المصدر: | International Journal for Parasitology: Drugs and Drug Resistance International Journal for Parasitology: Drugs and Drug Resistance, Vol 13, Iss, Pp 8-15 (2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Sulfotransferase, 030231 tropical medicine, Binding pocket, Schistosomiasis, Drug binding, Biology, Schistosoma japonicum, Article, lcsh:Infectious and parasitic diseases, Microbiology, Schistosomicides, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, polycyclic compounds, medicine, Animals, lcsh:RC109-216, Pharmacology (medical), Pharmacology, chemistry.chemical_classification, Molecular Structure, Schistosoma spp, Schistosoma mansoni, Prodrug, medicine.disease, biology.organism_classification, Oxamniquine, 030104 developmental biology, Infectious Diseases, Enzyme, chemistry, Schistosoma haematobium, Schistosoma, Parasitology, Sulfotransferases, medicine.drug |
| الوصف: | 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. Graphical abstract Image 1 Highlights • OXA can kill S. mansoni but not S. haematobium or S. japonicum. • S. mansoni whole worm homogenates activate OXA, while S. haematobium and S. japonicum homogenates do not. • Differences in SULT amino acid contacts do not abrogate OXA binding in S. haematobium but may affect binding in S. japonicum. • The ability of OXA or its derivative to fit in the binding pocket determines whether sulfation takes place and parasite killing results. |
| تدمد: | 2211-3207 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea4b04f1ba31d6275e8af4a1302037b6Test https://doi.org/10.1016/j.ijpddr.2020.04.001Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ea4b04f1ba31d6275e8af4a1302037b6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113207 |
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