GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase.
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.
Blackburn
A C
AC
Molecular Genetics Group, Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Coggan
M
M
Tzeng
H F
HF
Lantum
H
H
Polekhina
G
G
Parker
M W
MW
Anders
M W
MW
Board
P G
PG
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*
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