Insect Molecular Biology (2005) 14(1), 3–8

MINI REVIEW
Blackwell Publishing, Ltd.

Insect glutathione transferases and insecticide resistance

A. A. Enayati*, H. Ranson† and J. Hemingway† conjugated substrates (Habig et al., 1974). In addition, some
*School of Public Health, Mazandaran University of GSTs catalyse a dehydrochlorination reaction using reduced
Medical Sciences, Sari, Iran; and †Liverpool School of glutathione as a cofactor rather than a conjugate (Clark &
Tropical Medicine, Liverpool, UK Shamaan, 1984). GSTs are important in cancer epidemiology
and drug resistance (Tew, 1994; Hayes & Pulford, 1995) and
hence are well studied in mammals. The majority of studies
Abstract
on insect GSTs have focused on their role in detoxifying
Glutathione transferases (GSTs) are a diverse family foreign compounds, in particular insecticides and plant
of enzymes found ubiquitously in aerobic organisms. allelochemicals and, more recently, their role in mediating
They play a central role in the detoxification of both oxidative stress responses. (Clark et al., 1986; Wang et al.,
endogenous and xenobiotic compounds and are also 1991; Fournier et al., 1992; Ranson et al., 2001; Vontas
involved in intracellular transport, biosynthesis of et al., 2001; Sawicki et al., 2003).
hormones and protection against oxidative stress.
Interest in insect GSTs has primarily focused on their
Classification and nomenclature
role in insecticide resistance. GSTs can metabolize
insecticides by facilitating their reductive dehydro- There are at least two ubiquitously distributed distantly related
chlorination or by conjugation reactions with reduced groups of GSTs, classified according to their location within
glutathione, to produce water-soluble metabolites that the cell: microsomal and cytosolic. A third group of GSTs,
are more readily excreted. In addition, they contribute the Kappa class, are located in mammalian mitochondria
to the removal of toxic oxygen free radical species pro- and peroxisomes (Morel et al., 2004; Lander et al., 2004) and
duced through the action of pesticides. Annotation of are structurally distinct from the microsomal and cytosolic
the Anopheles gambiae and Drosophila melanogaster GSTs (Robinson et al., 2004). To date, genome data mining
genomes has revealed the full extent of this enzyme has failed to detect any members of this GST class in insects.
family in insects. This mini review describes the insect A single microsomal GST gene is present in the genome
GST enzyme family, focusing specifically on their role of the fruitfly Drosophila melanogaster whereas the mosquito
in conferring insecticide resistance. Anopheles gambiae has three microsomal GST genes (Toba
& Aigaki, 2000; Ranson et al., 2002). The microsomal GSTs
Keywords: insects, insecticide resistance, detoxification,
are trimeric, membrane-bound proteins. Although very
glutathione transferases.
different in structure and in origin, the microsomal GSTs
catalyse similar reactions to the cytosolic GSTs (Gakuta &
Introduction Toshiro, 2000; Prabhu et al., 2001). Microsomal GSTs have
not been implicated in the metabolism of insecticides and
The glutathione transferases (GSTs) are a large family of
will not be discussed further in this review.
multifunctional enzymes involved in the detoxification of a
Insect cytosolic GSTs were initially assigned numbers
wide range of xenobiotics including insecticides (Salinas &
according to their order of elution from the various purifica-
Wong, 1999). GSTs primarily catalyse the conjugation of
tion procedures employed or isoelectric points (Clark et al.,
electrophilic compounds with the thiol group of reduced
1985; Prapanthadara et al., 1993). Later two immunologi-
glutathione (GSH), generally making the resultant products
cally distinct classes of GSTs were recognized in house-
more water soluble and excretable than the non-GSH
flies and designated as class I and class II (Fournier et al.,
1992). The class II insect GSTs are encoded by a single
doi: 10.1111/j.1365-2583.2004.00529.x gene in all species studied to date (Beall et al., 1992; Reiss
Received 30 April 2004; accepted after revision 20 August 2004. Corre- & James, 1993; Synder et al., 1995) although two distinct
spondence: Dr Hilary Ranson, Vector Research Group, Liverpool School of
Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Tel.: +44 transcripts are produced by alternative splicing of the
(0)151 7053310; fax: +44 (0)151 3053369; e-mail: hranson@[Link] A. gambiae class II gene (Ding et al., 2003). The class I

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4 A. A. Enayati et al.

insect GSTs, in contrast, are encoded by a multigene family

in Anopheles mosquitoes, D. melanogaster and Musca
domestica (Toung et al., 1993; Zhou & Syvanen, 1997;
Ranson et al., 2002).
As the volume of insect sequence data increased, addi-
tional GSTs were identified that did not clearly fit within
class I or II and the mammalian system of GST nomencla-
ture was adopted whereby classes are designated using
Greek letters (Chelvanayagam et al., 2001). Phylogenetic
comparison of insect and mammalian GST genes showed
that the insect class II GSTs are orthologous to the Sigma
GST class found in a diverse range of species from net-
matodes to mammals (Agianian et al., 2003). In contrast,
the class I GSTs are unique to insects and were re-named
Delta GSTs. A second large class of GSTs, the Epsilon
class, is also restricted to insects (Ranson et al., 2001). The
Delta and Epsilon GST classes have expanded independ-
ently in D. melanogaster and A. gambiae, suggesting that
these enzymes play important roles in the adaptation of these
species to their specific environments (Ranson et al., 2002).
The majority of the remaining cytosolic insect GSTs are
members of the Zeta, Theta and Omega classes (Board
et al., 1997, 2000; Ranson et al., 2002). The relatively high
degree of conservation of these GST genes across taxa
suggests that they play essential steps in conserved phys-
iological pathways. The complete inventory of A. gambiae
cytosolic GSTs includes three genes, GSTu1, GSTu2 and
GSTu3, that cannot be readily assigned to the existing classes.
They share less than 40% amino acid idenitiy with other insect
GSTs and are physically separate from other members of the
GST gene family on the mosquito chromosomes (Ding
et al., 2003). These may represent novel classes of insect
GSTs but have been temporarily designated unclassified
(u). The phylogenetic relationship between the different
classes of GSTs found in insects is shown in Fig. 1.
By extending the mammalian GST classification system
to encompass insect GSTs the nomenclature of individual
insect GST genes and proteins has been clarified (Chel-
vanayagam et al., 2001). Individual GST subunits are now
Figure 1. Neighbor joining tree illustrating the relationship between the
assigned names indicating the species from which they were classes of GSTs found in insects. The amino acid sequence of all cytosolic
isolated and the GST class. They are also given a number GSTs from Anopheles gambiae and Drosophila melanogaster were aligned
that may reflect the order of discovery or the genome with GSTs from mammals, plants and nematodes from the Zeta, Sigma,
Omega and Theta classes using CLUSTALW. For clarity, a single GST peptide
organizations. For example, AgGSTd12 is the twelfth was selected for each class from the non-insect phyla (accession numbers
member of the A. gambiae Delta class of GST subunits and wormbase protein IDs: HsZeta, O43708; CeZeta, WP:Ce25559;
to be identified. The distribution of different classes of AtZeta, AF288182; CeSigma, WP:Ce04834; HsSigma, O60760; CeOmega,
WP:Ce15815; HsOmega, P78417; AtTheta, AJ131580; HsTheta, S44358).
GSTs in insects and other animals is shown in Table 1. The tree was constructed by the neighbor-joining method from a similarity
matrix of pair-wise comparisons made using the Jukes–Cantor algorithm
Bootsrap values (500 replicates) are shown at selected nodes. The nodes
Enzyme structure of highly supported insect GST classes have been collapsed. Those insect
GSTs whose classifcation is unresolved are shown in bold. Ag = Anopheles
Cytosolic GSTs are hetero- or homo-dimeric proteins gambiae; At = Arabidopsis thaliana; Ce = Caenorhabditis elegans;
approximately 25 kDa in size. The polypeptide chain of Dm = Drosophila melanogaster; Hs = Homo sapiens. See text for further
details.
each monomer folds into two domains joined by a variable
linker region. The N-terminal domain (residues 1– 80) con-
sists of four beta sheets and three flanking alpha helices

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Insect glutathione transferases 5

Table 1. Summary of insect GST classes

GST Putative transcript Putative transcript no.

class Distribution no. in A. gambiae in D. melanogaster Examples in other insect species

Delta Insects only 15 11 L. cuprina, M. domestica, N. lugens, C. variipennis

Epsilon Insects only 8 14 P. xylotstella, M. sexta, M. domestica
Omega Nematodes, insects, mammals 1 5
Theta Mammals, insects and plants 2 4
Sigma Molluscs, helminths, nematodes, 1 1 M. domestica, B. germanica, C. fumiferana, M. sexta
insects, mammals
Zeta Plants, nematodes. Insects, mammals 1 2

and adopts a conformation similar to the thioredoxin domain the insect-specific Delta and Epsilon classes, have resulted
found in many proteins that bind GSH or cysteine (see in expansions of the GST family. Because substitution of a
reviews by Dirr et al., 1994; Wilce & Parker, 1994; Sheehan small number of amino acids can have dramatic effects on
et al., 2001). This domain contains the majority of residues the substrate specificity of the enzymes (Ortelli et al.,
involved in the binding of glutathione (the G-site). The larger 2003), the process of gene duplication, diversification and
C-terminal domain consists of a variable number of alpha selection can tailor the repetoire of reactions catalysed by
helices. The variable hydrophobic H-site, which interacts with GSTs to suit the particular ecological niche occupied by a
the electrophilic substrates, is largely formed from residues species (Ranson et al., 2002).
in the C-terminal domain. Although each monomeric active Futher GST diversity is generated by alternative spicing
site functions independently, their quaternary structure is in Anopheles mosquitoes and genetic rearrangements
essential for their activity (Danielson & Mannervik, 1985). leading to gene fusions in Musca domestica. Two GST
genes are alternatively spliced in A. gambiae: four distinct
peptides with differing catalytic properties are generated
Mode of action
from the Delta class AgGSTD1 gene (Ranson et al., 1998)
In a GST-catalysed conjugation reaction, one molecule of and two transcripts, sharing two common 5′ exons but dif-
reduced GSH and one molecule of a second substrate are fering in their use of 3′ exons, are generated from the single
combined to form a thioester. The reaction proceeds via Sigma GST gene in this species (Ding et al., 2003). The
substrate binding, the activation of the thiol group of GSH genome of M. domestica contains multiple intronless
and subsequent nucleophilic attack by the anionic GSH on loci encoding Delta GSTs, some of which appear to have
the bound hydrophobic compound (Atkins et al., 1993). resulted from the fusion between the 5′ and 3′ ends of
This conjugation neutralizes the electrophilic sites of the different Delta GST genes. It is not known whether all of
lipophilic substrate and protects the cellular components, these housefly GST genes encode functional proteins
especially the nucleophilic oxygen and nitrogen of DNA but it is possible that a rare recombination mechanism
from electrophilic attack of nucleophiles. Conjugation also may be contributing to GST diversity in this species (Zhou
renders the product more water soluble and therefore more & Syvanen, 1997).
readily excretable from the cell.
GSTs have a high affinity towards GSH and because this
Regulation of GST expression
tripiptide is present at high intracellular concentrations the
GSH binding site of GST may always be occupied. The In non-insect species, many GST enzymes are differentially
‘active site residue’ in the N-terminal domain interacts with regulated in response to various inducers or environmental
and activates the sulphydryl group of glutathione. In most signals or in a tissue- or developmental-specific manner.
mammalian GSTs the active site residue is a tyrosine A similarly complex pattern of regulation is expected for
(Karshikoff et al., 1993; Wilce & Parker, 1994) but in the insect GSTs. Two review articles have described the effect
Delta and Epsilon insect GST classes this role is performed of various dietary compounds, insecticides and laboratory
by a serine residue (Board et al., 1995). inducers on general GST expression (Clark, 1989; Yu, 1996).
Now that the full extent of the GST family is known for two insect
species, more specific studies can be conducted to determine
Gene organization
the factors regulating expression of individual GST genes.
The diversity of reactions catalysed by GSTs is a function Levels of GST activity vary throughout the life stage of
of the broad substrate specificities of many individual GST insects. For example, in Aedes aegypti, total GST activity
enzymes and the extensive nature of the GST supergene measured with 1-chloro-2,4-dinitrobenzene (CDNB) and
family. In insects, local gene duplications, particularly within 1,2-dichloronitrobenzene (DCNB) increases during larval

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6 A. A. Enayati et al.

development, reaching its peak in the pupal stage and

declining in adults as they age (Hazelton & Laing, 1983). In
a preliminary investigation of the expression profiles of
A. gambiae GSTs, transcripts were detectable for all but
one of the genes in 1-day-old adults (Ding et al., 2003). No
attempt was made to quantify the expression level in different
developmental stages in A. gambiae but it is apparent from
studies in other insects that the levels of individual enzymes
can fluctuate widely during the lifespan of an insect. For
example, a Sigma GST from the spruce budworm, Choris- Figure 2. Model of DDT dehydrochlorinase activity of GSTs (after
Matsumura, 1985).
toneura fumiferana, is expressed at very low levels in feeding
larvae but high levels in diapausing larvae (Feng et al.,
1999). Increased rates of DDT dehydrochlorination confer resist-
Variations in the level of GST activity in different insect ance to DDT in many insect species including houseflies
tissues have been reported in several species. In cases where and the mosquitoes Ae. aegypti, A. gambiae and A. dirus
the variation in activity is attributed to individual enzymes, (Prapanthadara et al., 1993, 1996; Grant et al., 1991). In
such studies can provide valuable insights into the functions Ae. aegypti, two immunologically distinct forms of GST are
of different GSTs. Thus the finding that Sigma GSTs from overproduced in a DDT-resistant strain (Grant et al., 1991).
housefly and Drosophila were predominately located in Overexpression of at least one of these is thought to be
the indirect flight muscles, in association with troponin H, controlled by a mutation in a trans-acting repressor in the
suggested that the role of this GST class was structural DDT-resistant strain (Grant & Hammock, 1992) but the
rather than catalytic (subsequently, however, these GSTs nature of this repressor is not known. Multiple Epsilon class
have been found to play a very important role in protection GSTs from A. gambiae are overexpressed in a DDT-resistant
against oxidative stress) (Franciosa & Berge, 1995; Singh strain and one of these, GSTe2, encodes an enzyme that
et al., 2001). Very high levels of GST activity have been has the highest levels of DDT dehydrochlorinase activity
reported in the fat body and midguts of insects. Both these reported for any GST (Ortelli et al., 2003). Genetic mapping
tissues are important sites for the detoxification of xenobiotics. of the major loci conferring DDT resistance in A. gambiae
implicate both cis- and trans-acting factors in the over-
expression of the Epsilon class GSTs (Ranson et al., 2000).
GSTs and insecticide resistance
GSTs are responsible for many cases of organophos-
Elevated GST activity has been associated with resistance phate resistance (Hayes & Wolf, 1988). The conjugation of
to all the major classes of insecticides (Prapanthadara et al., glutathione to organophosphate insecticides results in their
1993; Huang et al., 1998; Vontas et al., 2001). In many cases, detoxification via two distinct pathways. In O-dealkylation,
the individual GST enzyme(s) involved in resistance have glutathione is conjugated with the alkyl portion of the insec-
not been identified and GSTs have been implicated by ticide, e.g. the demethylation of tetrachlorvinphos in resist-
association only (i.e. an increase in GST activity, detected ant houseflies (Oppenoorth et al., 1979). In the second
using model substrates, in insecticide-resistant strains of mechanism, O-dearylation, the glutathione reacts with the
insects vs. their susceptible counterparts). In cases that leaving group, e.g. the detoxification of parathion and
have been studied in more detail, resistance has been methyl parathion in the diamondback moth Plutella xylos-
attributed to increases in the amount of one or more GST tella (Chiang & Sun, 1993). Recombinant GST enzymes
enzymes, either as a result of gene amplification or more from the diamondback moth and housefly have verified the
commonly through increases in transcriptional rate, rather role of these enzymes in the metabolism of organophos-
than qualitative changes in individual enzymes (Grant & phate insecticides (Huang et al., 1998; Wei et al., 2001).
Hammock, 1992; Ranson et al., 2001). GSTs have not yet been implicated in the direct metabo-
Dehydrochlorination is an important mechanism for DDT lism of pyrethroid insecticides. Nevertheless, they may play
detoxification. This reaction is catalysed by GSTs (Clark & an important role in conferring resistance to this insecticide
Shamaan, 1984). The proposed mechanism is shown in class by detoxifying lipid peroxidation products induced by
Fig. 2. A GSH conjugate of DDT has never been identified, pyrethroids (Vontas et al., 2001). A Delta class GST has been
but this tripeptide is an essential cofactor in the reaction. cloned from a pyrethroid resistant strain of Nilaparvata lugens.
The thiolate anion generated in the active site of the GST The recombinant protein produced from this gene has high
acts as a general base and abstracts a hydrogen atom from peroxidase activity and it has been proposed that this
DDT resulting in the elimination of chlorine to generate enzyme is involved in the prevention or repair of oxidative
DDE. Other organochlorine insecticides, e.g. lindane, are damage induced by insecticide exposure (Vontas et al.,
detoxified by conjugation to glutathione. 2002). Elevated GSTs in other resistant insects may play a

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Insect glutathione transferases 7

similar role. GSTs may also protect against pyrethroid Clark, A.G. and Shamaan, N.A. (1984) Evidence that DDT-
toxicity in insects by sequestering the insecticide (Kostaro- dehydrochlorinase from the house fly is a glutathione S-
poulos et al., 2001). transferase. Pest Biochem Physiol 22: 249–261.
Clark, A.G., Shamaan, N.A., Sinclair, M.D. and Dauterman, W.C.
(1986) Insecticide metabolism by multiple glutathione S-
Summary transferases in two strains of the house fly, Musca domestica
(L.). Pest Biochem Physiol 25: 169 –175.
Advances in genetics and biochemistry have revealed the Danielson, U.H. and Mannervik, B. (1985) Kinetic independence of
complexity of the insect GST family. Specific functions of the subunits of cytosolic glutathione transferase from the rat.
some individual GSTs, particularly their role in detoxifying Biochem J 231: 263 –267.
xenobiotics, have been identified but much remains to be Ding, Y., Ortelli, F., Rossiter, L.C., Hemingway, J. and Ranson, H.
(2003) The Anopheles gambiae glutathione transferase super-
learnt about the endogenous substrates of insect GSTs.
gene family: annotation, phylogeny and expression profiles.
Deciphering the precise expression profile of each GST BMC Genomics 4: 35.
gene may provide clues to function that can subsequently Dirr, H., Reinemer, P. and Huber, R. (1994) X-ray crystal structures
be elucidated in in vitro systems. of cytosolic glutathione S-transferases. Implications for protein
architecture, substrate recognition and catalytic function. Eur J
Biochem 220: 645 – 661.
Acknowledgements Feng, Q.L., Davey, K.G., Pang, A.S.D., Primavera, M., Ladd, T.R.,
Zheng, S.C., Sohi, S.S., Retnakaran, A. and Palli, S.R. (1999)
This work was funded in part by a Royal Society Dorothy
Glutathione S-transferase from the spruce budworm, Chorstoneura
Hodgkin Fellowship (to H.R.) and a Wellcome Trust Project fumiferana: identification, characterization, localization, cDNA
Grant (to J.H. and H.R.). cloning and expression. Insect Biochem Mol Biol 29: 779 –793.
Fournier, D., Bride, J.M., Poire, M., Berge, J.B. and Plapp, F.W.
(1992) Insect glutathione S-transferases. Biochemical charac-
References
teristics of the major forms from houseflies susceptible and
Agianian, B., Tucker, P.A., Schouten, A., Leonard, K., Bullard, B. resistant to insecticides. J Biol Chem 267: 1840 –1845.
and Gros, P. (2003) Structure of a Drosophila Sigma class glu- Franciosa, H. and Berge, J.B. (1995) Glutathione S-transferases in
tathione S-transferase reveals a novel active site topography housefly (Musca domestica): location of GST-1 and GST-2 fam-
suited for lipid peroxidation products. J Mol Biol 326: 151–165. ilies. Insect Biochem Mol Biol 25: 311–317.
Atkins, W.M., Wang, R.W., Bird, A.W., Newton, D.J. and Lu, A.H.W. Gakuta, T. and Toshiro, A. (2000) Disruption of the microsomal
(1993) The catalytic mechanism of glutathione S-transferase glutathione S-transferase-like gene reduces life span of
(GST): spectroscopic determination of the pKa of Tyr-9 in rat Drosophila melanogaster. Gene 253: 179 –187.
alpha 1–1 GST. J Biol Chem 268: 19188–11991. Grant, D.F., Dietze, E.C. and Hammock, B.D. (1991) Glutathione S-
Beall, C., Fyrberg, C., Song, S. and Fyrberg, E. (1992) Isolation transferase isozymes in Aedes aegypti: purification, characteriza-
of a Drosophila gene encoding glutathione S-transferase. tion, and isozyme specific regulation. Insect Biochem 4: 421–433.
Biochem Genet 30: 515–527. Grant, D.F. and Hammock, B.D. (1992) Genetic and molecular evid-
Board, P.G., Baker, R.T., Chelvanayagam, G. and Jermiin, L.S. ence for a trans-acting regulatory locus controlling glutathione
(1997) Zeta, a novel class of glutathione transferase in a range S-transferase-2 expression in Aedes aegypti. Mol Gen Genet
of species from plants to humans. Biochem J 328: 929 – 935. 234: 169 –176.
Board, P.G., Coggan, M., Chelvanayagam, G., Easteal, S., Habig, W.H., Pabst, M.J. and Jakoby, W.B. (1974) Glutathione S-
Jermiin, L.S., Schulte, G.K., Danley, D.E., Hoth, L.R., Griffor, M.C., transferases. J Biol Chem 249: 7130 –7139.
Kamath, A.V., Rosner, M.H., Chrunyk, B.A., Perregaux, D.E., Hayes, J.D. and Pulford, D.J. (1995) The glutathione S-transferase
Gabel, C.A., Geoghegan, K.F. and Pandit, J. (2000) Identifica- supergene family – Regulation of GST and the contribution of
tion, characterization, and crystal structure of the Omega class the isoenzymes to cancer chemoprotection and drug resist-
glutathione transferases. J Biol Chem 275: 24798–24806. ance. Crit Rev Biochem Mol Biol 30: 445 – 600.
Board, P.G., Coggan, M., Wilce, M.C. and Parker, M.W. (1995) Evid- Hayes, J.D. and Wolf, C.R. (1988) Role of glutathione transferase
ence for an essential serine residue in the active site of the in drug resistance. In Glutathione Conjugation: Mechanisms
Theta class glutathione transferases. Biochem J 311: 247–250. and Biological Significance (Sies, H. and Ketterer, B., eds),
Chelvanayagam, G., Parker, M.W. and Board, P.G. (2001) Fly fish- pp. 315–355. Academic Press Ltd, London.
ing for GSTs: a unified nomenclature for mammalian and insect Hazelton, G.A. and Laing, C.A. (1983) Glutathione S-transferase
glutathione transferases. Chem Biol Interact 133: 256–260. activities in the yellow-fever mosquito [Aedes aegypti (Lois-
Chiang, F.-M. and Sun, C.-N. (1993) Glutathione transferase iso- ville)] during growth and aging. Biochem J 210: 281–287.
zymes of diamondback moth larvae and their role in the degra- Huang, H.S., Hu, N.T., Yao, Y.E., Wu, C.Y., Chiang, S.W. and Sun,
dation of some organophosphorus insecticides. Pest Biochem C.N. (1998) Molecular cloning and heterologous expression of
Physiol 45: 7–14. a glutathione S- transferase involved in insecticide resistance
Clark, A.G. (1989) The comparative enzymology of the glutathione from the diamondback moth, Plutella xylostella. Insect Bio-
S-transferases from non-vertabrate organisms. Comp Bio- chem Mol Biol 28: 651– 658.
chem Physiol 92: 419–446. Karshikoff, A., Reinemer, P., Huber, R. and Ladenstein, R. (1993)
Clark, A.G., Dick, G.L., Martindale, S.M. and Smith, J.N. (1985) Electrostatic evidence for the activation of the glutathione thiol
Glutathione S-transferases from the New Zealand grass grub, by Tyr7 in pi-class glutathione transferases. Eur J Biochem
Costelytra zealandica. Insect Biochem 15: 35– 44. 215: 663 – 670.

© 2005 The Royal Entomological Society, Insect Molecular Biology, 14, 3 – 8

 13652583, 2005, 1, Downloaded from [Link] by CAPES, Wiley Online Library on [21/10/2024]. See the Terms and Conditions ([Link] on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8 A. A. Enayati et al.

Kostaropoulos, I., Papadopoulos, A.I., Metaxakis, A., Boukouvala, E. Modelling and bioinformatics studies of the human Kappa-class
and Papadopoulou-Mourkidou, E. (2001) Glutathione S- glutathione transferase predict a novel third glutathione trans-
transferase in the defence against pyrethroids in insects. Insect ferase family with similarity to prokaryotic 2-hydroxychromene-
Biochem Mol Biol 31: 313–319. 2-carboxylate isomerases. Biochem J 379: 541– 552.
Lander, J.E., Parsons, J.F., Rife, C.L., Gilliland, G.L. and Armstrong, R.N. Salinas, A.E. and Wong, M.G. (1999) Glutathione S-transferases
(2004) Parallel evolutionary pathways for glutathione trans- – A review. Current Med Chem 6: 279 –309.
ferases: structure and mechanims of the mitochondrial class Sawicki, R., Singh, S.P., Mondal, A.K., Benes, H. and Zimniak, P.
Kappa enzyme rGSTK1–1. Biochemistry 43: 352–261. (2003) Cloning, expression and biochemical characterization of
Matsumura, F. (1985) Toxicology of Insecticides. Plenum Press, one Epsilon-class (GST-3) and ten Delta-class (GST-1) glutathione
New York. S-transferases from Drosophila melanogaster, and identification
Morel, F., Rauch, C., Petit, E., Piton, A., Theret, N., Coles, B. and of additional nine members of the Epsilon class. Biochem J
Guillouzo, A. (2004) Gene and protein characterization of the 370: 661– 669.
human glutathione S-transferase kappa and evidence for a Sheehan, D., Meade, G., Foley, V.M. and Dowd, C.A. (2001)
peroxisomal localization. J Biol Chem 279: 16246–16253. Structure, function and evolution of glutathione transferases:
Oppenoorth, F.J., Van der Pas, L.J.T. and Houx, N.W.H. (1979) implications for classification of non-mammalian members of
Glutathione S-transferase and hydrolytic activity in a an ancient enzyme superfamily. Biochem J 360: 1–16.
tetrachlorvinphos-resistant strain of housefly and their Singh, S.P., Coronella, J.A., Benes, H., Cochrane, B.J. and Zimniak, P.
influence on resistance. Pest Biochem Physiol 11: 176–188. (2001) Catalytic function of Drosophila melanogaster glutath-
Ortelli, F., Rossiter, L.C., Vontas, J., Ranson, H. and Hemingway, J. ione S-transferase DmGSTS1–1 (GST-2) in conjugation of lipid
(2003) Heterologous expression of four glutathione transferase peroxidation end products. Eur J Biochem 268: 2912–2923.
genes genetically linked to a major insecticide-resistance locus Synder, M.J., Walding, J.K. and Feyereisen, R. (1995) Glutathione
from the malaria vector Anopheles gambiae. Biochem J 373: S-transferases from larval Manduca sexta midgut: sequense of
957–963. two cDNAs and enzyme induction. Insect Biochem Mol Biol 25:
Prabhu, K.S., Reddy, P.V., Gmpricht, G., Hildenbrandt, G.R., 455 – 465.
Scholz, R.W., Sordillo, L.M. and Reddy, C.C. (2001) Microsomal Tew, K.D. (1994) Glutathione-associated enzymes in anticancer
glutathione S-transferase A1–1 with glutathione peroxidase drug resistance. Cancer Res 54: 4313 – 4320.
activity from sheep liver: molecular cloning, expression and Toba, G. and Aigaki, T. (2000) Disruption of the microsomal
characterization. Biochem J 360: 345–354. glutathione S-transferase-like gene reduces life span of
Prapanthadara, L., Hemingway, J. and Ketterman, A.J. (1993) Drosophila melanogaster. Gene 253: 179 –187.
Partial purification and characterization of glutathione S- Toung, Y.-P.S., Hsieh, T. and Tu, C.-P.D. (1993) The glutathione S-
transferase involved in DDT resistance from the mosquito transferase D genes: a divergently organized, intronless gene
Anopheles gambiae. Pest Biochem Physiol 47: 119–133. family in Drosophila melanogaster. J Biol Chem 268: 9737–
Prapanthadara, L., Koottathep, S., Promtet, N., Hemingway, J. and 9746.
Ketterman, A.J. (1996) Purification and characterization of a Vontas, J.G., Small, G.J. and Hemingway, J. (2001) Glutathione S-
major glutathione S-transferase from the mosquito Anopheles transferases as antioxidant defence agents confer pyrethroid
dirus (Species B). Insect Biochem Mol Biol 26: 277–285. resistance in Nilaparvata lugens. Biochem J 357: 65–72.
Ranson, H., Claudianos, C., Ortelli, F., Abgrall, C., Hemingway, J., Vontas, J.G., Small, G.J., Nikou, D.C., Ranson, H. and Heming-
Sharakhova, M.V., Unger, M.F., Collins, F.H. and Feyereisen, way, J. (2002) Purification, molecular cloning and heterologous
R. (2002) Evolution of supergene families associated with expression of a glutathione S-transferase involved in insecti-
insecticide resistance. Science 298: 179–181. cide resistance from the rice brown planthopper, Nilaparvata
Ranson, H., Collins, F. and Hemingway, J. (1998) The role of alter- lugens. Biochem J 362: 329 –337.
native mRNA splicing in generating heterogeneity within the Wang, J.Y., McCommas, S. and Syvanen, M. (1991) Molecular
Anopheles gambiae class I glutathione S-transferase family. cloning of a glutathione S-transferase overproduced in an
Proc Natl Acad Sci USA 95: 14284–14289. insecticide-resistant strain of the housefly (Musca domestica).
Ranson, H., Jensen, B., Wang, X., Prapanthadara, L., Hemingway, Mol Gen Genet 227: 260 – 266.
J. and Collins, F.H. (2000) Genetic mapping of two loci affecting Wei, S.H., Clark, A.G. and Syvanen, M. (2001) Identification and
DDT resistance in the malaria vector, Anopheles gambiae. cloning of a key insecticide-metabolizing glutathione S-
Insect Mol Biol 9: 499–507. transferase (MdGST-6A) from a hyper insecticide-resistant
Ranson, H., Rossiter, L., Ortelli, F., Jensen, B., Wang, X., Roth, strain of the housefly Musca domestica. Insect Biochem Mol
C.W., Collins, F.H. and Hemingway, J. (2001) Identification of a Biol 31: 1145 –1153.
novel class of insect glutathione S-transferases involved in Wilce, M.C.J. and Parker, M.W. (1994) Structure and function of
resistance to DDT in the malaria vector Anopheles gambiae. glutathione S-transferases. Biochem Biophys Acta 1205: 1–18.
Biochem J 359: 295–304. Yu, S.J. (1996) Insect gutathione S-transferases. Zool Studies 35:
Reiss, R.A. and James, A.A. (1993) A glutathione S-transferase 9 –19.
gene of the vector mosquito, Anopheles gambiae. Insect Mol Zhou, Z.H. and Syvanen, M. (1997) A complex glutathione trans-
Biol 2: 25 –32. ferase gene family in the housefly Musca domestica. Mol Gen
Robinson, A., Huttley, G.A., Booth, H.S. and Board, P.G. (2004) Genet 256: 187–194.

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