Biochemical analysis, gene structure and localization of the 24 kDa glutathione S-transferase from Onchocerca volvulus

Liebau, Eva; Wildenburg, Gabriele; Brophy, Peter M.; Walter, Rolf D.; Henkle‐Dührsen, Kimberly

doi:10.1016/0166-6851(96)02660-6

Cited by 42 publications

(27 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The other known OvGST with glutathione-binding capacity (OvGST2) shows a strong topological relationship with the pi class GSTs (34). However, in OvGST2, the C-terminal coil lies to one side of the active site.…”

Section: Resultsmentioning

confidence: 99%

“…However, in OvGST2, the C-terminal coil lies to one side of the active site. This coil normally forms the back face of the hydrophobic substrate binding pocket, and its displacement results in a "tunnel-like" hole (34). Direct comparison of the active sites of OvGST1 and OvGST2 shows that that of OvGST1 is more flattened, resulting in a wider and shallower cleft.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies demonstrate the participation of filarial GSTs in the defense against oxidative stress (34,35). The potential to protect the parasite against host immunity makes them attractive candidate vaccine antigens (11).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Structural Analysis and Antibody Response to the Extracellular GlutathioneS-Transferases fromOnchocerca volvulus

et al. 2001

Self Cite

View full text Add to dashboard Cite

Onchocerca volvulus is a human pathogenic filarial parasite which, like other parasitic nematodes, is capable of surviving in an immunologically competent host by employing a variety of immune evasion strategies and defense mechanisms including the detoxification and repair mechanisms of the glutathione S-transferases (GSTs). In this study we analyzed the glycosylation pattern and the immunological properties of extracellular O. volvulus GST1a and -1b (OvGST1a and -1b). The enzymes differ in only 10 amino acids, and both are glycoproteins that have cleavable signal peptides and unusual N-terminal extensions. These characteristics have not been described for other GSTs so far. Mass spectrometry analyses indicate that both enzymes carry high-mannose type oligosaccharides on at least four glycosylation sites. Glycosylation sites 1 to 3 of OvGST1a

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Structural Analysis and Antibody Response to the Extracellular GlutathioneS-Transferases fromOnchocerca volvulus

et al. 2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…The inhibitor profile of S. cervi GST showed a limited relationship to the profile of mammalian GST(s) (Stockman et al, 1987). The inhibitor profile of S. cervi GST is similar to that described for the Schistosoma mansoni (Sm28) GST (Walker et al, 1993), O. volvulus GST (OvGST2) (Liebau et al, 1996) and GST from Ascaris suum (Liebau et al, 1997). From the perspective of classification, it is interesting that, whereas helminth organisms express GST(s) that are clearly related to mu, pi and sigma classes of other organisms, these enzymes contain sufficient regions of structural difference compared with host enzymes to hold out the prospect of development of parasite-specific vaccines.…”

Section: Ellagic Acidmentioning

confidence: 55%

Inhibition of Filarial Glutathione-S-transferase by various classes of compounds and their evaluation as novel antifilarial agents

Ahmad

Srivastava

2008

Helminthologia

View full text Add to dashboard Cite

Glutathione S-transferase(s); GST(s) (E.C. 2.5.1.18) are a large family of multifunctional dimeric enzymes that conjugate reduced glutathione to electrophilic centres in hydrophobic organic compounds. GST(s) represent the major class of detoxifying enzymes from parasitic helminths. The GST enzymatic activity has been described in the adult and larval stages of helminths. Several forms and isoforms of the enzyme have been purified and GST genes have also been isolated and expressed as recombinant proteins. The helminth GST(s) participate in detoxification of lipid hydroperoxides and cytotoxic carbonyl compounds produced by oxygen-reactive intermediates (ORIs). The ORIs can come from the endogenous parasite metabolism or from the host immune system. The helminth GST(s) are able to conjugate glutathione to xenobiotic compounds or to bind to the anthelminth drugs. GST is usually found to be localized near to host-parasite interface. This enzyme has been identified as a potentially vulnerable target in immunotherapy and chemotherapy of parasitic diseases. The most effective drug candidates are those based on inhibitors of GST. In the present study, purified GST from cytosolic fraction of bovine filarial worms Setaria cervi was inhibited in a concentration dependent fashion by various compounds such as hemin, ethacrynic acid, S-hexylglutathione, quercetin, cibacron blue, lithocholate sulfate and ellagic acid. Cytosolic GST was inhibited to varying degrees by each inhibitor. In this context, the possible physiological significance of the observed results has been discussed.

show abstract

“…Because of their abundance in the infective stage larvae, they are more accessible to the immune system to become the potential targets for providing protective immunity. GSTs are postulated to protect the parasite against host-mediated lipid peroxidation of the membrane [33,34] and involved in the defense against oxidative stress [35,36]. Rao et al [37] reported that B. malayi GSTs are the major metabolic enzymes that play an important role in the parasite's survival.…”

Section: Discussionmentioning

confidence: 99%

Immunization with Wuchereria bancrofti Glutathione-S-transferase Elicits a Mixed Th1/Th2 Type of Protective Immune Response Against Filarial Infection in Mastomys

et al. 2016

View full text Add to dashboard Cite

Lymphatic filariasis is a mosquito borne parasitic infection and can severely affect the normal working ability of an individual. Currently there is no vaccine available to prevent this infection and the development of a potential vaccine could effectively support the on-going mass drug administration program by World Health Organization (WHO). Filarial parasites have complex mechanisms to modulate the host immune responses against them. The glutathione-S-transferases (GST) are the important enzymes effectively involved to counteract the oxidative free radicals produced by the host. In the present study, we have shown that the mastomys which are fully permissible rodents for Brugia malayi when immunized with Wuchereria bancrofti recombinant GST (rWbGST) could induce 65.5 % in situ cytotoxicity against B. malayi infective (L 3 ) larvae. There was a balanced Th1/Th2 immune response in the vaccinated animals, characterized by higher levels of WbGST-specific IgG1 and IgG2a antibodies and pronounced IFN-c, IL-10 and IL-4 cytokines production by the spleen cells.

show abstract

Biochemical analysis, gene structure and localization of the 24 kDa glutathione S-transferase from Onchocerca volvulus

Cited by 42 publications

References 33 publications

Structural Analysis and Antibody Response to the Extracellular GlutathioneS-Transferases fromOnchocerca volvulus

Structural Analysis and Antibody Response to the Extracellular GlutathioneS-Transferases fromOnchocerca volvulus

Inhibition of Filarial Glutathione-S-transferase by various classes of compounds and their evaluation as novel antifilarial agents

Immunization with Wuchereria bancrofti Glutathione-S-transferase Elicits a Mixed Th1/Th2 Type of Protective Immune Response Against Filarial Infection in Mastomys

Contact Info

Product

Resources

About