title: GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase.
abstract: The zeta class glutathione transferases (GSTs) are known to catalyse the isomerization of maleylacetoacetate (MAA) to fumarylacetoacetate (FAA), and the biotransformation of dichloroacetic acid to glyoxylate. A new allele of human GSTZ1, characterized by a Thr82Met substitution and termed GSTZ1d, has been identified by analysis of the expressed sequence tag (EST) database. In European Australians, GSTZ1d occurs with a frequency of 0.16. Like GSTZ1b-1b and GSTZ1c-1c, the new isoform has low activity with dichloroacetic acid compared with GSTZ1a-1a. The low activity appears to be due to a high sensitivity to substrate inhibition. The maleylacetoacetate isomerase (MAAI) activity of all known variants was compared using maleylacetone as a substrate. Significant differences in activity were noted, with GSTZ1a-1a having a notably lower catalytic efficiency. The unusual catalytic properties of GSTZ1a-1a in both reactions suggest that its characteristic arginine at position 42 plays a significant role in the regulation of substrate access and/or product release. The different amino acid substitutions have been mapped on to the recently determined crystal structure of GSTZ1-1 to evaluate and explain their influence on function.
authors.affiliation: Molecular Genetics Group, Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Blackburn
authors.forename: M
authors.initials: M
authors.lastname: Coggan
authors.forename: H F
authors.initials: HF
authors.lastname: Tzeng
authors.forename: H
authors.initials: H
authors.lastname: Lantum
authors.forename: G
authors.initials: G
authors.lastname: Polekhina
authors.forename: M W
authors.initials: MW
authors.lastname: Parker
authors.forename: M W
authors.initials: MW
authors.lastname: Anders
authors.forename: P G
authors.initials: PG
authors.lastname: Board
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001120:Arginine / Q000235:genetics; D005260:Female; D018698:Glutamic Acid; D005982:Glutathione Transferase / Q000235:genetics*; D005998:Glycine / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics; D008239:Lysine / Q000235:genetics; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011392:Proline / Q000235:genetics; D013912:Threonine / Q000235:genetics; D019745:cis-trans-Isomerases / Q000235:genetics*
chemical_list: D013912:Threonine; D018698:Glutamic Acid; D001120:Arginine; D011392:Proline; D008715:Methionine; C407705:GSTZ1 protein, human; D005982:Glutathione Transferase; D019745:cis-trans-Isomerases; C021531:maleylacetoacetate isomerase; D007930:Leucine; D008239:Lysine; D005998:Glycine