title: Topogenesis of glycolytic enzymes in Trypanosoma brucei.
abstract: The protozoan haemoflagellate Trypanosoma brucei, differs from other eukaryotic cells in that it contains nine enzymes involved in glucose and glycerol metabolism which are associated with microbody-like organelles called glycosomes. The information available to date indicates that glycosomal enzymes are synthesized as polypeptides of mature size. For three of them, glyceraldehyde-phosphate dehydrogenase, aldolase and glycerol-3-phosphate dehydrogenase, it has been shown that they are made on free polysomes in the cytosol and are subsequently transferred to the glycosome without any secondary modification. The topogenic signal responsible for import into the glycosome must, therefore, be present in the mature protein. Remarkable differences exist between the latter proteins and other glycolytic enzymes: (i) most glycosomal proteins have an apparent Mr which is 1-5 kDa larger than their homologous counterparts from the cytosol, or from other organisms; (ii) they have a high net positive charge. Based on the modelling of three glycosomal sequences in the respective homologous structures, it is thought that the topogenic signal may consist of a unique insertion, containing one or more basic amino acids which, together with additional positive charges elsewhere, constitute two positive hot spots approximately 4 nm apart on the surface of the protein. Such common elements, unique for the glycolytic enzymes from the Trypanosomatidae, lend themselves as excellent targets for the development of new drugs.
authors.affiliation: Research Unit for Tropical Diseases, International Institute of Cellular and Molecular Pathology, Brussels, Belgium.
authors.forename: F R
authors.initials: FR
authors.lastname: Opperdoes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004798:Enzymes / Q000235:genetics; D006019:Glycolysis; D008830:Microbodies / Q000201:enzymology; D008969:Molecular Sequence Data; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics
chemical_list: D004798:Enzymes