Structural evidence for three different types of glutathione transferase in human tissues

Ålin, Per; Mannervik, Bengt; Jörnvall, Hans

doi:10.1016/0014-5793(85)80324-0

Cited by 57 publications

(28 citation statements)

References 25 publications

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“…This is not substantially different from the first estimate ofthe subunit molecular weight for the basic human GST (25,000) (14). The amino acid composition calculated from the deduced sequence was found to be in good agreement with the previously published composition of the basic human GST (13). The amino acid sequence deduced from the XGST2-3 cDNA is rich in lysine and this is consistent with the relatively high pI of GST-2 isozymes (pH 8.5-9.0) (11).…”

Section: Resultssupporting

confidence: 86%

See 1 more Smart Citation

Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12.

Board¹,

Webb²

1987

Proc. Natl. Acad. Sci. U.S.A.

122

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The glutathione S-transferases (GST) (glutathione transferase; EC 2.5.1.18) are a family of enzymes responsible for the metabolism of a broad range of xenobiotics and carcinogens. A cDNA clone containing the entire amino acid coding sequence of a human GST-2 subunit has been isolated using a Xgtll expression library. The complete nudeotide sequence and a partial restriction map are presented. The subunit is composed of221 amino acids with a molecular weight of 25,425 before posttranslational modification. The deduced amino acid sequence is rich in lysine, which is consistent with the relatively high pI of GST-2. The human sequence shows considerable homology with the rat Ya and Yc GST sequences but little homology with the rat GSTp and Yb subunit sequences. Southern blots of restriction digests of human DNA indicate that there may be multiple GST-2 genes. In situ hybridization of the cloned cDNA to human chromosomes produces intense labeling only over band p12 on the short arm of chromosome 6 near the centromere. This indicates that the GST-2 gene(s) are located only at this site.The glutathione S-transferases (GST) (glutathione transferase; EC 2.5.1.18) are a family of multifunctional proteins involved in the metabolism of a broad range ofxenobiotics (1) and the binding and possible transport of some endogenous anionic compounds such as bilirubin and heme (2, 3). Deficiencies of GST have been implicated in the etiology of nonhemolytic unconjugated hyperbilirubinemia in the newborn and potentially increased susceptibility to chemical carcinogens (4,5).The genetic, developmental, and environmental factors regulating the expression of GST isozymes are complex. In man there are many GST isozymes that show variable expression between individuals, between tissues, and at different stages of development (6-9). Previous studies have shown that the human GST are the products of at least three distinct gene loci (GST-J, GST-2, GST-3) (6-8). A recent proposal has suggested that there are three evolutionary GST classes (,, a, 1r) that have been conserved between species (10). These classes may correspond to the three loci described in man.The GST-2 isozymes are basic and consist of a group of at least three isozymes that can be differentiated electrophoretically (6). These isozymes share many characteristics, including the same subunit molecular weight, glutathione peroxidase activity, and immunological identity (11).The GST-2 isozymes correspond to the basic GST isozymes characterized chromatographically on several occasions (12-14). The relationships between the GST-2 isozymes are not clear. There is contradictory evidence supporting the suggestions that they are either the posttranslationally modified products ofa single locus (7,8,14) or the products oftwo separate loci (15).To investigate further the genetic interrelationships within the human GST gene family we have undertaken a program to clone and map particular GST genes. We report here the isolation of a full-length cDNA for a GST-2 subunit, show the comp...

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Section: Resultssupporting

confidence: 86%

“…The GST-2 isozymes correspond to the basic GST isozymes characterized chromatographically on several occasions (12)(13)(14). The relationships between the GST-2 isozymes are not clear.…”

mentioning

confidence: 99%

Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12.

Board¹,

Webb²

1987

Proc. Natl. Acad. Sci. U.S.A.

122

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“…Notwithstanding the difficulties in identifying classes of glutathione transferase in different species, it was recently noted (4) that the amino-terminal amino acid sequences of two homologous mouse transferases (15) showed extensive similarities to those of two homologous rat transferases (16). This finding prompted studies of the glutathione transferase isoenzymes in mouse liver (17) and in human tissues (7), as well as an attempt at interspecies classification ofthe multiple forms of the enzyme (18). The present report correlates enzymatic and structural distinctions and shows that glutathione transferases from several species can be assigned to three classes comprising isoenzymes with common characteristic properties.…”

mentioning

confidence: 56%

Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties.

Mannervik¹,

Ålin²,

Guthenberg³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

947

518

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The major isoenzymes of cytosolic glutathione transferase (EC 2.5.1.18) from rat, mouse, and man are shown to share structural and catalytic properties that can be used for species-independent classification. Rat, mouse, and human isoenzymes were grouped with respect to aminoterminal amino acid sequences, after correlation of seven structures analyzed in the present investigation with structures determined earlier. The isoenzymes were also characterized by substrate specificities and sensitivities to inhibitors, and the data were subjected to pattern recognition analysis. In addition, the various isoenzymes were tested for cross-reactivity by immunoprecipitation with antibodies raised against rat and human transferases. The different types of data were clearly correlated and afforded an unambiguous division of the isoenzymes into three classes named alpha, mu, and pi. Each of the three mammalian species studied contains at least one isoenzyme of each class. It is suggested that the similarities of the isoenzymes in a class reflect evolutionary relationships and that the classification applies generally.

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“…On the basis of N-terminal sequence, substrate specificity and immunological properties three classes of cytosolic GST have been identified (class ce, /z, and zr) common to several mammalian species [3]. Human glutathione transferase class ~-is an acidic protein present in all human tissues so far investigated and it has been purified and extensively characterized from human placenta by different laboratories [4][5][6][7][8]. Recently, a complete primary structure has been reported, as deduced from the correspondent cDNA and the gene structure [9,10].…”

Section: Introductionmentioning

confidence: 99%

Identification of a highly reactive sulphydryl group in human placental glutathione transferase by a site‐directed fluorescent reagent

et al. 1990

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A fluorescent maleimide derivative, N-(4-anilino-l-naphthyl) maleimide (ANM), a specific probe for thiol groups, reacted with human placental glutathione transferase (GST, EC 2.5.1.18), causing a complete inactivation of the enzyme in a few minutes. The modified enzyme was denatured, alkylated and digested with (L-l-tosylamide-2-phenylethyl chloromethyl ketone)-trypsin. The tryptic digest was analysed by HPLC and a fluorescent peptide was obtained. The sequence of this peptide allowed us, by a comparison with a well known primary structure, to assign the position 47 to the most reactive cysteine of GST enzyme.

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Structural evidence for three different types of glutathione transferase in human tissues

Cited by 57 publications

References 25 publications

Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12.

Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12.

Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties.

Identification of a highly reactive sulphydryl group in human placental glutathione transferase by a site‐directed fluorescent reagent

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