Acetyl-CoA synthetase from the amitochondriate eukaryote Giardia lamblia belongs to the newly recognized superfamily of acyl-CoA synthetases (nucleoside diphosphate-forming)
Lb. Sanchez et al., Acetyl-CoA synthetase from the amitochondriate eukaryote Giardia lamblia belongs to the newly recognized superfamily of acyl-CoA synthetases (nucleoside diphosphate-forming), J BIOL CHEM, 275(8), 2000, pp. 5794-5803
The gene coding for the acetyl-CoA. synthetase (ADP-forming) from the amito
chondriate eukaryote Giardia lamblia has been expressed in Escherichia coli
. The recombinant enzyme exhibited the same substrate specificity as the na
tive enzyme, utilizing acetyl-CoA and adenine nucleotides as preferred subs
trates and less efficiently, propionyl- and succinyl-CoA. N- and C-terminal
parts of the G. lamblia acetyl-CoA sythetase sequence were found to be hom
ologous to the alpha- and beta-subunits, respectively, of succinyl-CoA synt
hetase, Sequence analysis of homologous enzymes from various bacteria archa
ea, and the eukaryote, Plasmodium fad ciparum, identified conserved feature
s in their organization, which allowed us to delineate a new superfamily of
acyl-CoA synthetases (nucleoside diphosphate-forming) and its signature mo
tifs, The representatives of this new superfamily of thiokinases vary in th
eir domain arrangement, some consisting of separate alpha- and beta-subunit
s and others comprising fusion proteins in alpha-beta or beta-alpha orienta
tion. The presence of homologs of acetyl synthetase (ADP-forming) in such h
uman pathogens as G. lamblia, Yersinia pestis, Bordetella pertussis, Pseudo
monas aeruginosa, Vibrio cholerae, Salmonella typhi, Porphyromonas gingival
is, and the malaria agent P. falciparum suggests that they might be used as
potential drug targets.