@article{1e864078264240beb2c354b69c9c7165,
title = "Why does oxamniquine kill Schistosoma mansoni and not S. haematobium and S. japonicum?",
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.",
keywords = "Drug binding, Oxamniquine, Schistosoma spp., Sulfotransferase",
author = "Rugel, {Anastasia R.} and Guzman, {Meghan A.} and Taylor, {Alexander B.} and Chevalier, {Fr{\'e}d{\'e}ric D.} and Tarpley, {Reid S.} and McHardy, {Stanton F.} and Xiaohang Cao and Holloway, {Stephen P.} and Anderson, {Timothy J.C.} and Hart, {P. John} and LoVerde, {Philip T.}",
note = "Funding Information: The research was supported by a grant to PTL and PJH from the NIH, NIAID R01 AI115691. PJH (AQ-1399) was funded by The Welch Foundation. Schistosome infected snails were provided by BRI via the NIAID schistosomiasis resource center under NIH-NIAID Contract No. HHSN272201000005I. The X-ray Crystallography Core Laboratory is a part of the Institutional Research Cores at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) supported by the Office of the Vice President for Research and the Mays Cancer Center (NIH P30 CA054174). This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41 GM103403). The Pilatus 6M detector on 24-ID-C beam line is funded by a NIH-ORIP HEI grant (S10 RR029205). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The research was supported by a grant to PTL and PJH from the NIH , NIAID R01 AI115691 . PJH (AQ-1399) was funded by The Welch Foundation . Schistosome infected snails were provided by BRI via the NIAID schistosomiasis resource center under NIH-NIAID Contract No. HHSN272201000005I. The X-ray Crystallography Core Laboratory is a part of the Institutional Research Cores at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) supported by the Office of the Vice President for Research and the Mays Cancer Center ( NIH P30 CA054174 ). This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines, which are funded by the National Institute of General Medical Sciences from the National Institutes of Health ( P41 GM103403 ). The Pilatus 6M detector on 24-ID-C beam line is funded by a NIH-ORIP HEI grant ( S10 RR029205 ). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = aug,
doi = "10.1016/j.ijpddr.2020.04.001",
language = "English (US)",
volume = "13",
pages = "8--15",
journal = "International Journal for Parasitology: Drugs and Drug Resistance",
issn = "2211-3207",
publisher = "Elsevier BV",
}