Structures of type 2 peroxisomal targeting signals in two trypanosomatid aldolases

Trypanosomatids, unicellular organisms responsible for several global disea ses, contain unique organelles called glycosomes in which the first seven g lycolytic enzymes are sequestered. We report the crystal structures of glyc osomal fructose-1,6-bisphosphate aldolase from two major tropical pathogens , Trypanosoma brucei and Leishmania mexicana, the causative agents of Afric an sleeping sickness and one form of leishmaniasis, respectively. Unlike ma mmalian aldolases, the T. brucei and L. mexicans aldolases contain nonameri c N-terminal type 2 peroxisomal targeting signals (PTS2s) to direct their i mport into the glycosome. In both tetrameric trypanosomatid aldolases, the PTS2s from two different subunits form two closely intertwined structures. These "PTS2 dimers", which have very similar conformations in the two aldol ase structures, are the first reported conformations of a glycosomal or per oxisomal PTS2 and provide opportunities for the design of trypanocidal comp ounds. (C) 2000 Academic Press.