title: A unique insertion in Plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: evolutionary and functional studies.
abstract: Plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (G6PD-6PGL) is a bifunctional enzyme with significant sequence similarity in both the 6PGL and G6PD domains to the Plasmodium falciparum enzyme. A recombinant form of the P. berghei enzyme was found to have both G6PD and 6PGL activities, and therefore catalyses the first two steps in the pentose phosphate pathway. Genes encoding very similar proteins are also found in three other malarial parasites, Plasmodium yoelii, Plasmodium chabaudi and Plasmodium knowlesi. All of these predicted enzymes contain unique parasite insertions in corresponding positions in the G6PD domain but the insertions differ in size and sequence. Such insertions are a common feature of malarial proteins but their origin and function is unknown. Excision of the insertion sequence in the P. berghei protein renders the G6PD domain inactive, although the 6PGL activity is unaffected. Replacing the insertion sequence in P. berghei with the insertion sequence from P. falciparum restores some of the G6PD activity and also enhances 6PGL activity. We conclude that although the insertions are evolving rapidly they have an essential role in the activity of the bifunctional enzyme.
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London W12 0NN, UK.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Clarke
authors.forename: Olugbemiro
authors.initials: O
authors.lastname: Sodeinde
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition; D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000502:physiology; D019143:Evolution, Molecular; D017353:Gene Deletion; D017125:Genes, Protozoan / Q000235:genetics; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010962:Plasmodium berghei / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: D005954:Glucosephosphate Dehydrogenase; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase