title: Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica.
abstract: Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member.
authors.affiliation: Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, SY23 2DA, UK.
authors.forename: Russell M
authors.initials: RM
authors.lastname: Morphew
authors.forename: Neil
authors.initials: N
authors.lastname: Eccleston
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Wilkinson
authors.forename: John
authors.initials: J
authors.lastname: McGarry
authors.forename: Samirah
authors.initials: S
authors.lastname: Perally
authors.forename: Mark
authors.initials: M
authors.lastname: Prescott
authors.forename: Deborah
authors.initials: D
authors.lastname: Ward
authors.forename: Diana
authors.initials: D
authors.lastname: Williams
authors.forename: Steve
authors.initials: S
authors.lastname: Paterson
authors.forename: M
authors.initials: M
authors.lastname: Raman
authors.forename: G
authors.initials: G
authors.lastname: Ravikumar
authors.forename: M
authors.initials: M
authors.lastname: Khalid Saifullah
authors.forename: S M
authors.initials: SM
authors.lastname: Abbas Abidi
authors.forename: Paul
authors.initials: P
authors.lastname: McVeigh
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Maule
authors.forename: Peter M
authors.initials: PM
authors.lastname: Brophy
authors.forename: E James
authors.initials: EJ
authors.lastname: LaCourse
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods; D003600:Cytosol / Q000201:enzymology; D015180:Electrophoresis, Gel, Two-Dimensional; D057075:Enzyme Assays; D004926:Escherichia coli / Q000235:genetics; D005209:Fasciola / Q000201:enzymology* / Q000235:genetics; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000235:genetics / Q000302:isolation & purification*; D015801:Helminth Proteins / Q000032:analysis*; D008969:Molecular Sequence Data; D010802:Phylogeny; D040081:Protein Array Analysis; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D014170:Transformation, Genetic
chemical_list: D015801:Helminth Proteins; D020543:Proteome; D011994:Recombinant Proteins; D005982:Glutathione Transferase