{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:19:55Z","timestamp":1770506395048,"version":"3.49.0"},"reference-count":35,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,5,15]]},"abstract":"<jats:p>GST (glutathione transferase) T1-1 plays an important role in the biotransformation of halogenated alkanes, which are used in large quantities as solvents and occur as environmental pollutants. Many reactions that are catalysed by GST T1-1 qualify as detoxification processes, but some reactions with dihalogenated alkanes lead to reactive products more toxic than the substrates. Murine GST T1-1 is particularly active with dichloromethane, which may explain the high carcinogenicity of dichloromethane in the mouse. Human GST T1-1 activity is considerably lower with halogenated hydrocarbons and some related substrates. Human GST T1-1 is polymorphic with a frequent null phenotype, suggesting that it is advantageous, under some circumstances, to lack the functional enzyme, which catalyses GSH conjugations that may cause bioactivation. The present study shows that amino acid residue 234 is a determinant of the differences in catalytic efficiency between the human and the rodent enzymes. The replacement of Trp234 in human GST T1-1 by arginine, found in the rodent enzyme, enhanced the alkyltransferase activity by an order of magnitude with a series of homologous iodoalkanes and some typical GST substrates. The specific activity of the alternative mutant Trp234\u2192Lys was lower than for the parental human GST T1-1 with many substrates, showing that a positive charge is not sufficient for increased activity. The enhanced activity of Trp234\u2192Arg with alkylating agents was dependent on the substrate tested, whereas no increase of the peroxidase activity with cumene hydroperoxide was noted. Residue 234 therefore is also involved in the control of the substrate selectivity of GST T1-1.<\/jats:p>","DOI":"10.1042\/bj20042064","type":"journal-article","created":{"date-parts":[[2005,5,10]],"date-time":"2005-05-10T16:27:42Z","timestamp":1115742462000},"page":"387-392","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Residue 234 in glutathione transferase T1-1 plays a pivotal role in the catalytic activity and the selectivity against alternative substrates"],"prefix":"10.1042","volume":"388","author":[{"given":"Abeer","family":"SHOKEER","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Uppsala University, Biomedical Center, Box 576, SE-751 23 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Karin","family":"LARSSON","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Uppsala University, Biomedical Center, Box 576, SE-751 23 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"MANNERVIK","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Uppsala University, Biomedical Center, Box 576, SE-751 23 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2005,5,10]]},"reference":[{"key":"2021112213263610800_B1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0378-4274(90)90094-3","article-title":"Biosynthesis, bioactivation, and mutagenicity of S-conjugates","volume":"53","author":"Dekant","year":"1990","journal-title":"Toxicol. Lett."},{"key":"2021112213263610800_B2","first-page":"21","article-title":"Purification, characterization and tissue distribution of human class theta glutathione S-transferase T1-1","volume":"39","author":"Juronen","year":"1996","journal-title":"Biochem. Mol. Biol. Int."},{"key":"2021112213263610800_B3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1042\/bj3260837","article-title":"Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human","volume":"326","author":"Sherratt","year":"1997","journal-title":"Biochem. J."},{"key":"2021112213263610800_B4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/BF00303122","article-title":"Metabolism of methyl chloride by human erythrocytes","volume":"63","author":"Peter","year":"1989","journal-title":"Arch. Toxicol."},{"key":"2021112213263610800_B5","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1042\/bj2740409","article-title":"Theta, a new class of glutathione transferases purified from rat and man","volume":"274","author":"Meyer","year":"1991","journal-title":"Biochem. J."},{"key":"2021112213263610800_B6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/096032719101000105","article-title":"Distribution of ethylene oxide in human blood and its implications for biomonitoring","volume":"10","author":"F\u00f6st","year":"1991","journal-title":"Hum. Exp. Toxicol."},{"key":"2021112213263610800_B7","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1021\/tx00045a019","article-title":"Enhancement of bacterial mutagenicity of bifunctional alkylating agents by expression of mammalian glutathione S-transferase","volume":"8","author":"Thier","year":"1995","journal-title":"Chem. Res. Toxicol."},{"key":"2021112213263610800_B8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1042\/bj3320097","article-title":"Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases","volume":"332","author":"Hurst","year":"1998","journal-title":"Biochem. J."},{"key":"2021112213263610800_B9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0009-2797(78)90076-5","article-title":"The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I. Activation through conjugation with glutathione in vitro","volume":"20","author":"Rannug","year":"1978","journal-title":"Chem. Biol. Interact."},{"key":"2021112213263610800_B10","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1073\/pnas.80.17.5266","article-title":"Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA","volume":"80","author":"Ozawa","year":"1983","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112213263610800_B11","doi-asserted-by":"crossref","first-page":"8576","DOI":"10.1073\/pnas.90.18.8576","article-title":"Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes","volume":"90","author":"Thier","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112213263610800_B12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/protein\/gzh005","article-title":"Directed enzyme evolution guided by multidimensional analysis of substrate-activity space","volume":"17","author":"Larsson","year":"2004","journal-title":"Protein Eng. Des. Sel."},{"key":"2021112213263610800_B13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/(SICI)1097-0134(19981115)33:3<444::AID-PROT12>3.0.CO;2-8","article-title":"A homology model for the human theta-class glutathione transferase T1-1","volume":"33","author":"Flanagan","year":"1998","journal-title":"Proteins"},{"key":"2021112213263610800_B14","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1006\/abbi.1997.0357","article-title":"Kinetic characterization of recombinant human glutathione transferase T1-1, a polymorphic detoxication enzyme","volume":"348","author":"Jemth","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"2021112213263610800_B15","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1042\/bj2820505","article-title":"Design of two chimaeric human-rat class alpha glutathione transferases for probing the contribution of C-terminal segments of protein structure to the catalytic properties","volume":"282","author":"Bj\u00f6rnestedt","year":"1992","journal-title":"Biochem. J."},{"key":"2021112213263610800_B16","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature (London)"},{"key":"2021112213263610800_B17","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1042\/bj1180765","article-title":"Formation of mercapturic acids in rats after the administration of aralkyl esters","volume":"118","author":"Clapp","year":"1970","journal-title":"Biochem. J."},{"key":"2021112213263610800_B18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0076-6879(81)77053-8","article-title":"Assays for differentiation of glutathione S-transferases","volume":"77","author":"Habig","year":"1981","journal-title":"Methods Enzymol."},{"key":"2021112213263610800_B19","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1042\/bj1210667","article-title":"The reaction of aralkyl sulphate esters with glutathione catalysed by rat liver preparations","volume":"121","author":"Gillham","year":"1971","journal-title":"Biochem. J."},{"key":"2021112213263610800_B20","doi-asserted-by":"crossref","first-page":"8733","DOI":"10.1074\/jbc.M211776200","article-title":"Identification of residues in glutathione transferase capable of driving functional diversification in evolution: a novel approach to protein redesign","volume":"278","author":"Ivarsson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021112213263610800_B21","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/0006-291X(76)90747-6","article-title":"Glutathione peroxidase activity in selenium-deficient rat liver","volume":"71","author":"Lawrence","year":"1976","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112213263610800_B22","first-page":"11048","article-title":"Catalytic mechanism of dichloromethane dehalogenase from Methylophilus sp","volume":"42","author":"Stourman","year":"2003","journal-title":"strain DM11. Biochemistry"},{"key":"2021112213263610800_B23"},{"key":"2021112213263610800_B24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0969-2126(98)00034-3","article-title":"Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site","volume":"6","author":"Rossjohn","year":"1998","journal-title":"Structure"},{"key":"2021112213263610800_B25","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1042\/bj2860929","article-title":"Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate","volume":"286","author":"Hussey","year":"1992","journal-title":"Biochem. J."},{"key":"2021112213263610800_B26","doi-asserted-by":"crossref","first-page":"9982","DOI":"10.1021\/bi983065b","article-title":"Fast product formation and slow product release are important features in a hysteretic reaction mechanism of glutathione transferase T2-2","volume":"38","author":"Jemth","year":"1999","journal-title":"Biochemistry"},{"key":"2021112213263610800_B27","first-page":"36","article-title":"Biochemical genetics of glutathione-S-transferase in man","volume":"33","author":"Board","year":"1981","journal-title":"Am. J. Hum. Genet."},{"key":"2021112213263610800_B28","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3891\/acta.chem.scand.34b-0607","article-title":"Identification of a new glutathione S-transferase in human liver","volume":"34","author":"Warholm","year":"1980","journal-title":"Acta Chem. Scand. Ser. B"},{"key":"2021112213263610800_B29","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/0006-291X(81)90870-6","article-title":"Purification of a new glutathione S-transferase (transferase mu) from human liver having high activity with benzo(\u03b1)pyrene-4,5-oxide","volume":"98","author":"Warholm","year":"1981","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112213263610800_B30","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1073\/pnas.85.19.7293","article-title":"Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion","volume":"85","author":"Seideg\u00e5rd","year":"1988","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021112213263610800_B31","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1124\/mol.52.6.958","article-title":"Characterization of a human glutathione S-transferase mu cluster containing a duplicated GSTM1 gene that causes ultrarapid enzyme activity","volume":"52","author":"McLellan","year":"1997","journal-title":"Mol. Pharmacol."},{"key":"2021112213263610800_B32","first-page":"460","article-title":"Interindividual variability of glutathione transferase expression","volume-title":"Interindividual Variability in Human Drug Metabolism","author":"Johansson","year":"2001"},{"key":"2021112213263610800_B33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/taap.2002.9348","article-title":"Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicity","volume":"179","author":"Sherratt","year":"2002","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"2021112213263610800_B34","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1007\/s002040050552","article-title":"Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney","volume":"72","author":"Thier","year":"1998","journal-title":"Arch. Toxicol."},{"key":"2021112213263610800_B35","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1042\/bj3350619","article-title":"Increased bioactivation of dihaloalkanes in rat liver due to induction of class theta glutathione S-transferase T1-1","volume":"335","author":"Sherratt","year":"1998","journal-title":"Biochem. J."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/388\/1\/387\/723327\/bj3880387.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/388\/1\/387\/723327\/bj3880387.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T14:08:22Z","timestamp":1637590102000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/388\/1\/387\/42083\/Residue-234-in-glutathione-transferase-T1-1-plays"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,10]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,5,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20042064","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,10]]}}}