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. 1997 Dec 15;328(Pt 3):929–935. doi: 10.1042/bj3280929

Zeta, a novel class of glutathione transferases in a range of species from plants to humans.

P G Board 1, R T Baker 1, G Chelvanayagam 1, L S Jermiin 1
PMCID: PMC1219006  PMID: 9396740

Abstract

Sequence alignment and phylogenetic analysis has identified a new subgroup of glutathione S-transferase (GST)-like proteins from a range of species extending from plants to humans. This group has been termed the Zeta class. An atomic model of the N-terminal domain suggests that the members of the Zeta class have a similar structure to that of other GSTs, binding glutathione in a similar orientation in the G site. Recombinant human GSTZ1-1 has been expressed in Escherichia coli and characterized. The protein is a dimer composed of 24.2 kDa subunits and has minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1, 3-diazole. Although low in comparison with other GSTs, GSTZ1-1 has glutathione peroxidase activity with t-butyl and cumene hydroperoxides. The members of the Zeta class have been conserved over a long evolutionary period, suggesting that they might have a role in the metabolism of a compound that is common in many living cells.

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Selected References

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  1. Baker R. T., Smith S. A., Marano R., McKee J., Board P. G. Protein expression using cotranslational fusion and cleavage of ubiquitin. Mutagenesis of the glutathione-binding site of human Pi class glutathione S-transferase. J Biol Chem. 1994 Oct 14;269(41):25381–25386. [PubMed] [Google Scholar]
  2. Blocki F. A., Ellis L. B., Wackett L. P. MIF protein are theta-class glutathione S-transferase homologs. Protein Sci. 1993 Dec;2(12):2095–2102. doi: 10.1002/pro.5560021210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Board P. G. Biochemical genetics of glutathione-S-transferase in man. Am J Hum Genet. 1981 Jan;33(1):36–43. [PMC free article] [PubMed] [Google Scholar]
  4. Board P. G., Coggan M., Wilce M. C., Parker M. W. Evidence for an essential serine residue in the active site of the Theta class glutathione transferases. Biochem J. 1995 Oct 1;311(Pt 1):247–250. doi: 10.1042/bj3110247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Board P. G., Coggan M., Wilce M. C., Parker M. W. Evidence for an essential serine residue in the active site of the Theta class glutathione transferases. Biochem J. 1995 Oct 1;311(Pt 1):247–250. doi: 10.1042/bj3110247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Board P., Coggan M., Johnston P., Ross V., Suzuki T., Webb G. Genetic heterogeneity of the human glutathione transferases: a complex of gene families. Pharmacol Ther. 1990;48(3):357–369. doi: 10.1016/0163-7258(90)90054-6. [DOI] [PubMed] [Google Scholar]
  7. Brophy P. M., Southan C., Barrett J. Glutathione transferases in the tapeworm Moniezia expansa. Biochem J. 1989 Sep 15;262(3):939–946. doi: 10.1042/bj2620939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chelvanayagam G., Wilce M. C., Parker M. W., Tan K. L., Board P. G. Homology model for the human GSTT2 Theta class glutathione transferase. Proteins. 1997 Jan;27(1):118–130. doi: 10.1002/(sici)1097-0134(199701)27:1<118::aid-prot12>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  9. Gillham B. The reaction of aralkyl sulphate esters with glutathione catalysed by rat liver preparations. Biochem J. 1971 Feb;121(4):667–672. doi: 10.1042/bj1210667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayes J. D., Pulford D. J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445–600. doi: 10.3109/10409239509083491. [DOI] [PubMed] [Google Scholar]
  11. Hiratsuka A., Sebata N., Kawashima K., Okuda H., Ogura K., Watabe T., Satoh K., Hatayama I., Tsuchida S., Ishikawa T. A new class of rat glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters as metabolites of carcinogenic arylmethanols. J Biol Chem. 1990 Jul 15;265(20):11973–11981. [PubMed] [Google Scholar]
  12. Hussey A. J., Hayes J. D. Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate. Biochem J. 1992 Sep 15;286(Pt 3):929–935. doi: 10.1042/bj2860929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Itzhaki H., Woodson W. R. Characterization of an ethylene-responsive glutathione S-transferase gene cluster in carnation. Plant Mol Biol. 1993 Apr;22(1):43–58. doi: 10.1007/BF00038994. [DOI] [PubMed] [Google Scholar]
  14. Ji X., Zhang P., Armstrong R. N., Gilliland G. L. The three-dimensional structure of a glutathione S-transferase from the mu gene class. Structural analysis of the binary complex of isoenzyme 3-3 and glutathione at 2.2-A resolution. Biochemistry. 1992 Oct 27;31(42):10169–10184. doi: 10.1021/bi00157a004. [DOI] [PubMed] [Google Scholar]
  15. Ji X., von Rosenvinge E. C., Johnson W. W., Tomarev S. I., Piatigorsky J., Armstrong R. N., Gilliland G. L. Three-dimensional structure, catalytic properties, and evolution of a sigma class glutathione transferase from squid, a progenitor of the lens S-crystallins of cephalopods. Biochemistry. 1995 Apr 25;34(16):5317–5328. doi: 10.1021/bi00016a003. [DOI] [PubMed] [Google Scholar]
  16. Jones D. T., Taylor W. R., Thornton J. M. The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci. 1992 Jun;8(3):275–282. doi: 10.1093/bioinformatics/8.3.275. [DOI] [PubMed] [Google Scholar]
  17. Lai H. C., Li N., Weiss M. J., Reddy C. C., Tu C. P. The nucleotide sequence of a rat liver glutathione S-transferase subunit cDNA clone. J Biol Chem. 1984 May 10;259(9):5536–5542. [PubMed] [Google Scholar]
  18. Lim K., Ho J. X., Keeling K., Gilliland G. L., Ji X., Rüker F., Carter D. C. Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV. Protein Sci. 1994 Dec;3(12):2233–2244. doi: 10.1002/pro.5560031209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M. K., Warholm M., Jörnvall H. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7202–7206. doi: 10.1073/pnas.82.21.7202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mannervik B., Awasthi Y. C., Board P. G., Hayes J. D., Di Ilio C., Ketterer B., Listowsky I., Morgenstern R., Muramatsu M., Pearson W. R. Nomenclature for human glutathione transferases. Biochem J. 1992 Feb 15;282(Pt 1):305–306. doi: 10.1042/bj2820305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mannervik B., Danielson U. H. Glutathione transferases--structure and catalytic activity. CRC Crit Rev Biochem. 1988;23(3):283–337. doi: 10.3109/10409238809088226. [DOI] [PubMed] [Google Scholar]
  22. Meyer D. J., Coles B., Pemble S. E., Gilmore K. S., Fraser G. M., Ketterer B. Theta, a new class of glutathione transferases purified from rat and man. Biochem J. 1991 Mar 1;274(Pt 2):409–414. doi: 10.1042/bj2740409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meyer R. C., Jr, Goldsbrough P. B., Woodson W. R. An ethylene-responsive flower senescence-related gene from carnation encodes a protein homologous to glutathione S-transferases. Plant Mol Biol. 1991 Aug;17(2):277–281. doi: 10.1007/BF00039505. [DOI] [PubMed] [Google Scholar]
  24. NASH T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J. 1953 Oct;55(3):416–421. doi: 10.1042/bj0550416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pemble S. E., Taylor J. B. An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. Biochem J. 1992 Nov 1;287(Pt 3):957–963. doi: 10.1042/bj2870957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pemble S. E., Wardle A. F., Taylor J. B. Glutathione S-transferase class Kappa: characterization by the cloning of rat mitochondrial GST and identification of a human homologue. Biochem J. 1996 Nov 1;319(Pt 3):749–754. doi: 10.1042/bj3190749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reinemer P., Dirr H. W., Ladenstein R., Schäffer J., Gallay O., Huber R. The three-dimensional structure of class pi glutathione S-transferase in complex with glutathione sulfonate at 2.3 A resolution. EMBO J. 1991 Aug;10(8):1997–2005. doi: 10.1002/j.1460-2075.1991.tb07729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Reinemer P., Dirr H. W., Ladenstein R., Schäffer J., Gallay O., Huber R. The three-dimensional structure of class pi glutathione S-transferase in complex with glutathione sulfonate at 2.3 A resolution. EMBO J. 1991 Aug;10(8):1997–2005. doi: 10.1002/j.1460-2075.1991.tb07729.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Reinemer P., Prade L., Hof P., Neuefeind T., Huber R., Zettl R., Palme K., Schell J., Koelln I., Bartunik H. D. Three-dimensional structure of glutathione S-transferase from Arabidopsis thaliana at 2.2 A resolution: structural characterization of herbicide-conjugating plant glutathione S-transferases and a novel active site architecture. J Mol Biol. 1996 Jan 19;255(2):289–309. doi: 10.1006/jmbi.1996.0024. [DOI] [PubMed] [Google Scholar]
  30. Ricci G., Caccuri A. M., Lo Bello M., Pastore A., Piemonte F., Federici G. Colorimetric and fluorometric assays of glutathione transferase based on 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Anal Biochem. 1994 May 1;218(2):463–465. doi: 10.1006/abio.1994.1209. [DOI] [PubMed] [Google Scholar]
  31. Simons P. C., Vander Jagt D. L. Purification of glutathione S-transferases from human liver by glutathione-affinity chromatography. Anal Biochem. 1977 Oct;82(2):334–341. doi: 10.1016/0003-2697(77)90169-5. [DOI] [PubMed] [Google Scholar]
  32. Sinning I., Kleywegt G. J., Cowan S. W., Reinemer P., Dirr H. W., Huber R., Gilliland G. L., Armstrong R. N., Ji X., Board P. G. Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes. J Mol Biol. 1993 Jul 5;232(1):192–212. doi: 10.1006/jmbi.1993.1376. [DOI] [PubMed] [Google Scholar]
  33. Soares M. B., Bonaldo M. F., Jelene P., Su L., Lawton L., Efstratiadis A. Construction and characterization of a normalized cDNA library. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9228–9232. doi: 10.1073/pnas.91.20.9228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stenberg G., Board P. G., Mannervik B. Mutation of an evolutionarily conserved tyrosine residue in the active site of a human class Alpha glutathione transferase. FEBS Lett. 1991 Nov 18;293(1-2):153–155. doi: 10.1016/0014-5793(91)81174-7. [DOI] [PubMed] [Google Scholar]
  35. Tan K. L., Chelvanayagam G., Parker M. W., Board P. G. Mutagenesis of the active site of the human Theta-class glutathione transferase GSTT2-2: catalysis with different substrates involves different residues. Biochem J. 1996 Oct 1;319(Pt 1):315–321. doi: 10.1042/bj3190315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Toung Y. P., Hsieh T. S., Tu C. P. The glutathione S-transferase D genes. A divergently organized, intronless gene family in Drosophila melanogaster. J Biol Chem. 1993 May 5;268(13):9737–9746. [PubMed] [Google Scholar]
  38. Wilce M. C., Board P. G., Feil S. C., Parker M. W. Crystal structure of a theta-class glutathione transferase. EMBO J. 1995 May 15;14(10):2133–2143. doi: 10.1002/j.1460-2075.1995.tb07207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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