Insect glutathione transferases

Ketterman, Albert J.; Saisawang, Chonticha; Wongsantichon, Jantana

doi:10.3109/03602532.2011.552911

Cited by 154 publications

(126 citation statements)

References 87 publications

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“…This gene family is particularly interesting because it is involved in human disease and exists in a wide range of species (Board 2011). However, research concerning GSTOs has mainly focused on mammals, and there is limited information on GSTO in insects (Ketterman et al 2011). In this study, we described the cloning and characterisation of a novel GSTO from A. cerana cerana.…”

Section: Discussionmentioning

confidence: 99%

“…The various insect GSTs play protective roles through different defence mechanisms. The insect-specific Delta-class and Epsilon-class GSTs are thought to be major contributors to detoxification and insecticide resistance (Ketterman et al 2011). In addition, some Epsilon-class GSTs in mosquito have peroxidase activity and may be important in protection against oxidative stress (Lumjuan et al 2005;Ortelli et al 2003).…”

Section: Discussionmentioning

confidence: 99%

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A novel Omega-class glutathione S-transferase gene in Apis cerana cerana: molecular characterisation of GSTO2 and its protective effects in oxidative stress

Zhang

Yan

et al. 2013

Cell Stress and Chaperones

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Oxidative stress may be the most significant threat to the survival of living organisms. Glutathione S-transferases (GSTs) serve as the primary defences against xenobiotic and peroxidative-induced oxidative damage. In contrast to other well-defined GST classes, the Omega-class members are poorly understood, particularly in insects. Here, we isolated and characterised the GSTO2 gene from Apis cerana cerana (AccGSTO2). The predicted transcription factor binding sites in the AccGSTO2 promoter suggested possible functions in early development and antioxidant defence. Real-time quantitative PCR (qPCR) and western blot analyses indicated that AccGSTO2 was highly expressed in larvae and was predominantly localised to the brain tissue in adults. Moreover, AccGSTO2 transcription was induced by various abiotic stresses. The purified recombinant AccGSTO2 exhibited glutathione-dependent dehydroascorbate reductase and peroxidase activities. Furthermore, it could prevent DNA damage. In addition, Escherichia coli overexpressing AccGSTO2 displayed resistance to long-term oxidative stress exposure in disc diffusion assays. Taken together, these results suggest that AccGSTO2 plays a protective role in counteracting oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel Omega-class glutathione S-transferase gene in Apis cerana cerana: molecular characterisation of GSTO2 and its protective effects in oxidative stress

Zhang

Yan

et al. 2013

Cell Stress and Chaperones

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“…The GSTs are another large family of metabolic enzymes encoded by a complex multi-gene family in insects. GSTs are now classified into several classes (z, u, s, and v) and are found in both the vertebrate (deuterostome) and the arthropod (protostome) branches of the evolutionary tree, suggesting fundamental roles in basic metabolism along with their ability to confer resistance to insecticides (Ketterman et al 2011). Analysis of DDT-resistant insects was again fundamental in increasing our understanding of the precise role of GSTs in resistance.…”

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confidence: 99%

The Molecular Genetics of Insecticide Resistance

2013

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The past 60 years have seen a revolution in our understanding of the molecular genetics of insecticide resistance. While at first the field was split by arguments about the relative importance of mono-vs. polygenic resistance and field-vs. laboratory-based selection, the application of molecular cloning to insecticide targets and to the metabolic enzymes that degrade insecticides before they reach those targets has brought out an exponential growth in our understanding of the mutations involved. Molecular analysis has confirmed the relative importance of single major genes in target-site resistance and has also revealed some interesting surprises about the multi-gene families, such as cytochrome P450s, involved in metabolic resistance. Identification of the mutations involved in resistance has also led to parallel advances in our understanding of the enzymes and receptors involved, often with implications for the role of these receptors in humans. This Review seeks to provide an historical perspective on the impact of molecular biology on our understanding of resistance and to begin to look forward to the likely impact of rapid advances in both sequencing and genome-wide association analysis."Curiouser and curiouser!" cried Alice.Lewis Carroll L ewis Carroll sent Alice down a rabbit hole without the least idea of what was to happen next, but as Alice ventured deeper into Wonderland things became "Curiouser and curiouser!" So indeed have studies on the molecular basis of insecticide resistance. While starting with rather simplistic expectations about the role of single mutations in single genes, resistance has been shown to involve a panoply of multiple mutations in multiple genes, often with independent and complex origins. This review will attempt to place these current findings into context and to examine the extent to which the field has often been historically blindsided by dogma. My arguments will encompass key controversies debated in the field such as the relative importance of mono-vs. polygenic resistance and the implications of resistance-associated mutations for whole-organism fitness in the absence of pesticide. Importantly, we will also examine the role of dogma in shaping the way that resistance research has been pursued over the past 50 years. Key questions addressed are therefore: How many mutations per gene cause resistance? How many mechanisms are there per species (genome)? How many independent genetic origins (mutations) give rise to each mechanism? What new mechanisms are still undiscovered and how might they arise? Monogenic vs. Polygenic ResistanceCrow, DDT, and DrosophilaThe humble fruit fly Drosophila melanogaster has been a key tool in unlocking the molecular basis of insecticide resistance, and early studies by James Crow and others have helped to establish Drosophila as a genetic model for resistance studies. Studies of DDT resistance in Drosophila have also typified arguments surrounding mono-vs. polygenic inheritance of insecticide resistance. In his pioneering review of in...

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“…65, 68 On the basis of the structural similarity and evolutionary proximity between the Delta and Epsilon classes, the proposed mechanism is also plausible for AgGSTE2 and AgGSTE5. 69 In the X-ray structure of AgGSTE2, the thiol group of GSH is within hydrogen-bond distance of the hydroxyl group of Ser12, which is thought to be required for the correct orientation and stabilization of the deprotonated thiolate anion in the active site (Figure 1). 19,65,66 Early in the simulations of AgGSTE2-I114T/F120L and AgGSTE5, the thiol group moves away from Ser12 and approaches the carboxylate group of Glu116 (Figure 8).…”

Section: Interactions Of Residues In the G-site Upon Gsh Bindingmentioning

confidence: 99%

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

Pontes¹,

Maia²,

Lima³

et al. 2016

Journal of the Brazilian Chemical Society

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Glutathione S-transferases (GSTs) are enzymes capable of metabolizing cytotoxic compounds. The enzyme AgGSTE2, member of epsilon class GSTs (GSTE), is the most important GST conferring resistance to dichloro-diphenyl-trichloroethane (DDT) in Anopheles gambiae. We have investigated the conformational dynamics of three GSTE variants (GSTE2, GSTE2-I114T/F120L, GSTE5) from A. gambiae. Large-scale motions of helices H2 and H4 and conformational transition of the C-terminal governs the opening of the G-site and is expected to affect substrate binding and product release. This structural rearrangement places Glu116 (Glu120 in GSTE5) close of the thiol group of the tripeptide glutathione (GSH) cofactor, making this residue a candidate to act as a base in the activation of DDT. The structural rearrangement is noticeable for AgGSTE2-F120L, which has been shown to confer increased DDT-resistance. The other variants exhibit a more subtle rearrangement. These findings corroborate the hypothesis that the increase of the conformational dynamics of GST Epsilon class isoforms from A. gambiae promotes higher DDTase activity.Keywords: molecular dynamics simulation, evolutional constraint, positive and negative selection, metabolic resistance, malaria vector IntroductionGlutathione transferases (EC 2.5.1.18) are highly promiscuous proteins where broad functional promiscuity co-exists with highly conserved structural fold. Glutathione S-transferases (GSTs) constitute a large family of cytosolic and membrane-bound proteins that catalyze the nucleophilic addition of the tripeptide glutathione (GSH) to a variety of electrophilic toxins and drugs (xenobiotics), leading to their excretion. 1,2 Lately, several other activities have also been associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, doublebond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic ligand binding and transport activity. 3 These polymorphic enzymes belong to supergene families whose members are generated by punctual mutations, gene duplication and alternative splicing. 4 The GST family is subdivided into several classes accordingly to its occurrence in different taxa.The number of isoforms per class varies widely, ranging from one to forty. 4 A single GST isoform is capable of conjugating glutathione to several hydrophobic substrates. Such promiscuity when coupled with the large number of isozymes generates a large range of potential substrates.Insects exhibit at least six classes of GSTs (Sigma, Omega, Theta, Zeta, Delta and Epsilon) with the first four classes present in almost all living organisms. 4,5 The Epsilon and Delta classes are arthropod specific and some members of these classes have been associated to insecticide resistance in culicid vectors. 5,6 The metabolism of toxic compounds in insects is conducted by a series of enzymes from different phases and GSTs act in phase II. GSTs metabolize these compounds in two ways: one has been cited above (through GSH conjugation) and the oth...

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Insect glutathione transferases

Cited by 154 publications

References 87 publications

A novel Omega-class glutathione S-transferase gene in Apis cerana cerana: molecular characterisation of GSTO2 and its protective effects in oxidative stress

A novel Omega-class glutathione S-transferase gene in Apis cerana cerana: molecular characterisation of GSTO2 and its protective effects in oxidative stress

The Molecular Genetics of Insecticide Resistance

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

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