Heme transport and detoxification in nematodes: subproteomics evidence of differential role of glutathione transferases

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dc.contributor.author Perally, Samirah
dc.contributor.author LaCourse, E. James
dc.contributor.author Campbell, Alison M.
dc.contributor.author Brophy, Peter M.
dc.date.accessioned 2009-05-21T11:36:34Z
dc.date.available 2009-05-21T11:36:34Z
dc.date.issued 2008-08-23
dc.identifier.citation Perally , S , LaCourse , E J , Campbell , A M & Brophy , P M 2008 , ' Heme transport and detoxification in nematodes: subproteomics evidence of differential role of glutathione transferases ' Journal of Proteome Research , vol 7 , no. 10 , pp. 4557-4565 . , 10.1021/pr800395x en
dc.identifier.issn 1535-3893
dc.identifier.other PURE: 103689
dc.identifier.other dspace: 2160/2316
dc.identifier.uri http://hdl.handle.net/2160/2316
dc.description Perally, S., LaCourse, E. J., Campbell, A. M., Brophy, P. M. (2008). Heme transport and detoxification in nematodes: subproteomics evidence of differential role of glutathione transferases. Journal of Proteome Research, 7, (10), 4557-4565. C. elegans is a functional genomics model for studying related parasitic nematodes of veterinary importance. All nematodes are are heme auxotrophs, requiring pathways for the uptake and transport of exogenous heme for incorporation into hemoproteins. The pathways represents are a target area for therapy. The paper identified delineated the roles of members of the glutathione transferase (GST) superfamily in heme biology by sub-proteomic and biochemical approaches, and a new form of heme binding GST was identified and characterised. The major contributor to experimental design, manuscript write-up and NERC grant holder/PhD supervisor (SP) at Aberystywyth. On file IMPF: 05.68 Sponsorship: Natural Environment Research Council and Aberystwyth University en
dc.description.abstract In contrast to their mammalian hosts, parasitic nematodes are heme auxotrophs and require pathways for the uptake and transport of exogenous heme for incorporation into hemoproteins. Phase II detoxification Nu-class glutathione transferase (GST) proteins have a proposed role as heme-binding ligandins in parasitic nematodes. The genome-verified free-living nematode Caenorhabditis elegans also cannot synthesize heme and is an ideal functional genomics model to delineate the role of individual nematode GSTs in heme trafficking and heme detoxification. In this study, C, elegans was exposed to externally controlled heme concentrations ranging from 20-fold suboptimal growth levels to 10-fold supra-optimal growth levels to mimic fluctuations in blood- and tissue-feeding parasitic cousins from the same nematode group. A new heme-responsive GST (GST-19) was identified by subproteomics approaches. Functional characterization of this and two other C. elegans GSTs revealed that they all have high affinity for heme compounds similar to mammalian soluble heme carrier proteins such as HBP23 (K-d approximate to 10(-8) M). In the genomics-predicted absence of orthologous mammalian soluble heme-binding proteins in nematodes, we propose that Nu-class GSTs are candidates in the cellular processing of heme compounds. Toxic heme binding may be coupled to enzymatic protection from its breakdown as several GSTs possess glutathione peroxidase activity. en
dc.format.extent 9 en
dc.language.iso eng
dc.relation.ispartof Journal of Proteome Research en
dc.subject glutathione transferase en
dc.subject heme en
dc.subject transport en
dc.subject detoxification en
dc.subject Caenorhabditis elegans en
dc.subject nematode en
dc.title Heme transport and detoxification in nematodes: subproteomics evidence of differential role of glutathione transferases en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1021/pr800395x
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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