Evaluation of the non-catalytic binding function of Ts26GST a glutathione transferase isoform of Taenia solium

Plancarte, A.; Romero, José R.; Nava, Gabriela; Reyes, Humberto; Hernández, Magdalena

doi:10.1016/j.exppara.2014.02.004

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…Ts26GST also recognized the trans - trans -2,4-dienal series utilized in this study, but as a ligandin (Plancarte et al ., 2014); whether Ts26GST conjugates GSH, similarly to TcGST1 and TCGST2, is unknown. Moreover, whether T. crassiceps GSTs possess ligandin functions remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…TcGST1 was more than 2000-fold less sensitive than TcGST2 to all tested inhibitors with the exception of Hm; however, the IC 50 values of CB, BST, RB and indomethacin for the TcGST1 and TcGST2 isoenzymes are similar to those of mammalian enzymes. Notably, TcGST1 was most highly inhibited by the mammalian enzyme Hm (Mannervik, 1985) and was 38-fold more sensitive than Ts26GST (Plancarte et al ., 2014). Additionally, TcGST1 inhibited Hm in a non-competitive manner, as did Ts26GST, but with higher affinity.…”

Section: Discussionmentioning

confidence: 99%

“…GSTs detoxify a variety of electrophilic compounds, including oxidized lipids, DNA and catechol products generated by ROS-induced damage to intracellular molecules. Additionally, GSTs detoxify a number of toxic ligands by acting as a non-catalytic, intracellular, binding protein (Sheehan et al ., 2001; Plancarte et al ., 2014).…”

Section: Introductionmentioning

confidence: 99%

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Two glutathione transferase isoforms isolated from juvenile cysts ofTaenia crassiceps: identification, purification and characterization

2017

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We identified and characterized the first two glutathione transferases (GSTs) isolated from juvenile cysts of Taenia crassiceps (EC 2.5.1.18). The two glutathione transferases (TcGST1 and TcGST2) were purified in a single-step protocol using glutathione (GSH)-sepharose chromatography in combination with a GSH gradient. The specific activities of TcGST1 and TcGST2 were 26 U mg-1 and 19 U mg-1, respectively, both at 25°C and pH 6.5 with 1-chloro-2,4-dinitrobenzene (CDNB) and GSH as substrates. The Km(CDNB) and Kcat(CDNB) values for TcGST1 and TcGST2 (0.86 μm and 62 s-1; 1.03 μm and 1.97 s-1, respectively) and Km(GSH) and Kcat(GSH) values for TcGST1 and TcGST2 (0.55 μm and 11.61 s-1; 0.3 μm and 32.3 s-1, respectively) were similar to those reported for mammalian and helminth GSTs. Mass spectrometry analysis showed that eight peptides from each of the two parasite transferases were a match for gi|29825896 glutathione transferase (Taenia solium), confirming that both enzymes are GSTs. The relative molecular masses were 54,000 ± 0.9 for the native enzymes and 27,500 ± 0.5 for the enzyme subunits. Thus, TcGST1 and TcGST2 are dimeric proteins. Optimal TcGST1 and TcGST2 activities were observed at pH 8.5 in the range of 20-55°C and pH 7.5 at 35-40°C, respectively. TcGST1 and TcGST2 were inhibited by cibacron blue (CB), bromosulphophthalein (BST), rose bengal (RB), indomethacin and haematin (Hm) with 50% inhibitory concentrations (IC50) in the μm range. TcGST1 was inhibited in a non-competitive manner by all tested inhibitors with the exception of indomethacin, which was uncompetitive. The discovery of these new GSTs facilitates the potential use of T. crassiceps as a model to investigate multifunctional GSTs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Two glutathione transferase isoforms isolated from juvenile cysts ofTaenia crassiceps: identification, purification and characterization

2017

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“…GST catalyzes the conjugation reaction between the electrophilic center of various classes of substrates and the sulfur atom of reduced glutathione to generate water-soluble glutathione conjugate that can be easily excreted [2]. Furthermore, GSTs were also found to bind several other exogenous and endogenous compounds in a non-catalytic fashion, thereby helping in various cellular processes [3]. They occur in almost all living organisms, including plants, animals, fungi, and bacteria [4].…”

Section: Introductionmentioning

confidence: 99%

Cytosolic Glutathione S-transferase in Bacteria: A Review

Shehu¹,

Abdullahi²,

Alias³

2018

Pol. J. Environ. Stud.

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Cytosolic glutathione S-transferase in bacteria possesses the biochemical capacity to degrade various classes of organochlorine pollutants in the environment in addition to their primary role of defending the organism from a wide range of endobiotics and xenobiotic substrates. Furthermore, the ability of different classes of cGST to recognize a wide repertoire of substrates due the variability in the substrate binding site of the enzymes makes them well suited for bioremediation purposes. cGSTs act as dehalogenases promoting a rapid degradation of various organochlorine compounds. Dehalogenation served as the primary mechanism for detoxification of various organochlorine compounds, making them vulnerable to attack by other degradative enzymes. However, despite their potential and advantage of wide substrate specificity, cGSTs have not been exploited for bioremediation purposes. In this review, we described the various cGST classes in bacteria and their phylogenetic relationships. Furthermore, the review reiterated that cGSTs in bacteria are involved in dehalogenation reaction, and this property can be harnessed for bioremediation of a diverse class of organochlorine pollutants as they currently represent the largest class of pollutants in the environment.

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“…parasite cGSTs [20]. Ts26GST has ligandin activity and is internalized by macrophages, suggesting an important role in transport and the parasite-host relationship [72,73].…”

Section: Structural Similarity Of Ts26gst To Human Cgstsmentioning

confidence: 99%

Development of New Drugs to TreatTaenia soliumCysticercosis: Targeting 26 kDa Glutathione Transferase

Zubillaga¹,

Jiménez²,

García-Gutiérrez³

et al. 2021

Current State of the Art in Cysticercosis and Neurocysticercosis

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Taenia solium causes neurocysticercosis, a parasitic infection of the central nervous system in humans. The costs of management, treatment, and diagnosis of patients with neurocysticercosis are high, and some patients do not respond to the currently available treatments. Helminth cytosolic glutathione transferases (GSTs) are essential enzymes involved in the regulation of immune responses, transport, and detoxification. In T. solium, three cytosolic GSTs with molecular masses of 26.5 (Ts26GST), 25.5 (Ts25GST), and 24.3 kDa (TsMσGST), classified as mu-alpha, mu and sigma GST-classes, respectively, constitute the main detoxification system, and they may be immune targets for the development of vaccines and new anthelmintics. We performed a successful virtual screen, and identified I7, a novel selective inhibitor of Ts26GST that showed a non-competitive inhibition mechanism towards substrate glutathione with a Ki of 55.7 mM and mixed inhibition towards the electrophilic substrate 1-chloro-2,4-dinitrobenzene with a Ki of 8.64 mM. Docking simulation studies showed that I7 can bind to a site that is adjacent to the electrophilic site and the furthest from the glutathione site. This new inhibitor of Ts26GST will be used as a lead molecule to develop new effective and safe drugs against diseases caused by T. solium.

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Evaluation of the non-catalytic binding function of Ts26GST a glutathione transferase isoform of Taenia solium

Cited by 8 publications

References 49 publications

Two glutathione transferase isoforms isolated from juvenile cysts ofTaenia crassiceps: identification, purification and characterization

Two glutathione transferase isoforms isolated from juvenile cysts ofTaenia crassiceps: identification, purification and characterization

Cytosolic Glutathione S-transferase in Bacteria: A Review

Development of New Drugs to TreatTaenia soliumCysticercosis: Targeting 26 kDa Glutathione Transferase

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