Glutathione transferases in the genomics era: New insights and perspectives

Frova, Carla

doi:10.1016/j.bioeng.2006.05.020

Cited by 432 publications

(372 citation statements)

References 129 publications

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“…GST gene encodes the glutathione S-transferases (GSTs) which play a key role in detoxification of a wide range of exogenous and endogenous compounds, such as carcinogens, therapeutic drugs, environmental toxins and reactive oxygen species [6]. GSTs are divided into three families: cytosolic, mitochondrial, and the membrane-associated proteins in eicosanoid and glutathione metabolism proteins, among them, the cytosolic subfamily is by far the most abundant one [7]. Numbers of studies have suggested that the genetic polymorphism of cytosolic GST genes was associated with the risk of RSA [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Zong

Sha

Xiang

et al. 2014

J Assist Reprod Genet

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Objective Recurrent spontaneous abortion (RSA) is a multifactor and distressing disease. There are still approximately half of the RSA patients with cause not being identified to date. Accumulating studies have confirmed that genetic polymorphisms in glutathione S-transferases (GSTs) were associated with the risk of recurrent spontaneous abortion. In this study, we aimed to investigate the relationship between the polymorphism of GSTA1, which is GSTA1 -69C/T (rs3957357), and the development of recurrent spontaneous abortion.Methods A case-control study of 127 cases with RSA and 112 ethnic and age matched women as controls was conducted. And measurement of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed to genotype all of samples in order to analyze the association between GSTA1 -69C/T (rs3957357) and the risk of RSA. Results We found that the frequencies of genotypes between cases and controls have no significant difference (P=0.908) and GSTA1 mutant allele GSTA1 −69 T was present at a frequency of 0.122 in case group, while in controls the frequency was 0.125 (P=0.922). Conclusion The polymorphism of GSTA1 (rs3957357) may not be associated with the risk of recurrent spontaneous abortion in Chinese Han population.

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Section: Introductionmentioning

confidence: 99%

Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Zong

Sha

Xiang

et al. 2014

J Assist Reprod Genet

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“…Detoxification enzymes are used widely to detect pollution in aquatic environments, and include the glutathione-stransferases (GSTs) which comprising a superfamily of multifunctional proteins with fundamental roles in the detoxification of a wide range of compounds (Frova, 2006, Davies, 1985, Bainy et al, 2000. Additionally, peroxidase and isomerase activities have been described for GST enzymes, enabling their use as biomarkers for oxidative stress (Sheehan et al, 2001).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Biological responses to contaminants in the Humber Estuary: Disentangling complex relationships

García‐Alonso

Greenway

Munshi

et al. 2011

Marine Environmental Research

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Due to the ecological importance of estuaries, it is necessary to understand the biological effects that potentially toxic contaminants induce in bioindicator species. A key aspect is whether effects at lower levels of biological organisation transfer through the system to higher levels. In understanding such processes, characterising multivariate relationships between contaminants, sediment toxicities and detoxification processes are important. Worms (Hediste diversicolor) and sediments were collected along the Humber Estuary, England, and inorganic and organic contaminants were quantified. Sediment toxicities and glutathione S-transferases (GSTs) activity in the ragworm were analysed. Concentrations of metals were highest near urban and industrial areas, whereas organic contaminants appeared at upstream locations. GST activity correlated with heavy metals. The genotoxicity, estrogenicity, dioxin and dioxin-like activity were higher at upstream locations. Estrogenicity correlated with alkylphenols and some organochlorines, whilst genotoxicity correlated with organochlorines and heavy metals. Despite this, higher level biological responses could not be predicted, indicating that homeostasis is operating.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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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Glutathione transferases in the genomics era: New insights and perspectives

Cited by 432 publications

References 129 publications

Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Biological responses to contaminants in the Humber Estuary: Disentangling complex relationships

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

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