X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment
dc.contributor.author | Line, K | |
dc.contributor.author | Isupov, MN | |
dc.contributor.author | LaCourse, EJ | |
dc.contributor.author | Cutress, DJ | |
dc.contributor.author | Morphew, RM | |
dc.contributor.author | Brophy, PM | |
dc.contributor.author | Littlechild, JA | |
dc.date.accessioned | 2019-02-28T13:47:42Z | |
dc.date.issued | 2019-01-29 | |
dc.description.abstract | Sigma class GST (Prostaglandin D synthase), FhGST-S1, is present in the excretory–secretory products (ES) of the liver fluke parasite Fasciola hepatica as cargo of extracellular vesicles (EVs) released by the parasite. FhGST-S1 has a well characterised role in the modulation of the immune response; a key fluke intercession that allows for establishment and development within their hosts. We have resolved the three-dimensional structure of FhGST-S1 in complex with its co-factor glutathione, in complex with a glutathione-cysteine adduct, and in a glutathione disulfide complex in order to initiate a research pipeline to mechanistically understand how FhGST-S1 functions within the host environment and to rationally design selective inhibitors. The overall fold of FhGST-S1 shows high structural similarity to other Sigma class GSTs. However, a unique interdomain disulfide bond was found in the FhGST-S1 which could stabilise the structure within the host gastro-intestinal environment. The position of the two domains of the protein with respect to each other is seen to be crucial in the formation of the active site cleft of the enzyme. The interdomain disulfide bond raises the possibility of oxidative regulation of the active site of this GST protein. | en_GB |
dc.description.sponsorship | European Union FP6 | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | NRN Wales | en_GB |
dc.description.sponsorship | University of Exeter | en_GB |
dc.identifier.citation | Vol. 9, article 902 | en_GB |
dc.identifier.doi | 10.1038/s41598-018-37531-5 | |
dc.identifier.grantnumber | BBH0092561 | en_GB |
dc.identifier.grantnumber | BB/L002035/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/36129 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.rights | © Te Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-02-28T13:47:42Z | |
dc.description | This is the final version. Available on open access from Nature Research via the DOI in this record | en_GB |
dc.description | Data delivery: The structure factors and the refined coordinates of the FhGST-S1 structures have been deposited with the Protein Data Bank and have the access codes 2WB9 and 2WDU. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2018-12-05 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2018-12-05 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-02-28T13:43:10Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-02-28T13:47:48Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © Te Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.