EUKARYOTIC TRANSLATION ELONGATION-FACTOR 1-GAMMA CONTAINS A GLUTATHIONE TRANSFERASE DOMAIN - STUDY OF A DIVERSE, ANCIENT PROTEIN SUPERFAMILY USING MOTIF SEARCH AND STRUCTURAL MODELING
Ev. Koonin et al., EUKARYOTIC TRANSLATION ELONGATION-FACTOR 1-GAMMA CONTAINS A GLUTATHIONE TRANSFERASE DOMAIN - STUDY OF A DIVERSE, ANCIENT PROTEIN SUPERFAMILY USING MOTIF SEARCH AND STRUCTURAL MODELING, Protein science, 3(11), 1994, pp. 2045-2054
Using computer methods for multiple alignment, sequence motif search,
and tertiary structure modeling, we show that eukaryotic translation e
longation factor 1 gamma (EF1 gamma) contains an N-terminal domain rel
ated to class theta glutathione S-transferases (GST). GST-Iike protein
s related to class theta comprise a large group including, in addition
to typical GSTs and EF1 gamma, stress-induced proteins from bacteria
and plants, bacterial reductive dehalogenases and beta-etherases, and
several uncharacterized proteins. These proteins share 2 conserved seq
uence motifs with GSTs of other classes (alpha, mu, and pi). Tertiary
structure modeling showed that in spite of the relatively low sequence
similarity, the GST-related domain of EF1 gamma is likely to form a f
old very similar to that in the known structures of class alpha, mu, a
nd pi GSTs. One of the conserved motifs is implicated in glutathione b
inding, whereas the other motif probably is involved in maintaining th
e proper conformation of the GST domain. We predict that the GST-like
domain in EF1 gamma is enzymatically active and that to exhibit GST ac
tivity, EF1 gamma has to form homodimers. The GST activity may be invo
lved in the regulation of the assembly of multisubunit complexes conta
ining EF1 and aminoacyl-tRNA synthetases by shifting the balance betwe
en glutathione, disulfide glutathione, thiol groups of cysteines, and
protein disulfide bonds. The GST domain is a widespread, conserved enz
ymatic module that may be covalently or noncovalently complexed with o
ther proteins. Regulation of protein assembly and folding may be 1 of
the functions of GST.