Biomaterial Database

A unique insertion in Plasmodium berghei glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: evolutionary and functional studies. 2003

Julia L Clarke, and Olugbemiro Sodeinde, and Philip J Mason

Department of Haematology, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London W12 0NN, UK.

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.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010962	Plasmodium berghei	A protozoan parasite of rodents transmitted by the mosquito Anopheles dureni.	Plasmodium bergheus,berghei, Plasmodium
D002265	Carboxylic Ester Hydrolases	Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.	Carboxylesterases,Ester Hydrolases, Carboxylic,Hydrolases, Carboxylic Ester
D005954	Glucosephosphate Dehydrogenase		Glucose-6-Phosphate Dehydrogenase,Dehydrogenase, Glucose-6-Phosphate,Dehydrogenase, Glucosephosphate,Glucose 6 Phosphate Dehydrogenase
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001482	Base Composition	The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.	Base Ratio,G+C Composition,Guanine + Cytosine Composition,G+C Content,GC Composition,GC Content,Guanine + Cytosine Content,Base Compositions,Base Ratios,Composition, Base,Composition, G+C,Composition, GC,Compositions, Base,Compositions, G+C,Compositions, GC,Content, G+C,Content, GC,Contents, G+C,Contents, GC,G+C Compositions,G+C Contents,GC Compositions,GC Contents,Ratio, Base,Ratios, Base
D016254	Mutagenesis, Insertional	Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.	Gene Insertion,Insertion Mutation,Insertional Activation,Insertional Mutagenesis,Linker-Insertion Mutagenesis,Mutagenesis, Cassette,Sequence Insertion,Viral Insertional Mutagenesis,Activation, Insertional,Activations, Insertional,Cassette Mutagenesis,Gene Insertions,Insertion Mutations,Insertion, Gene,Insertion, Sequence,Insertional Activations,Insertional Mutagenesis, Viral,Insertions, Gene,Insertions, Sequence,Linker Insertion Mutagenesis,Mutagenesis, Linker-Insertion,Mutagenesis, Viral Insertional,Mutation, Insertion,Mutations, Insertion,Sequence Insertions
D016415	Sequence Alignment	The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.	Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D017125	Genes, Protozoan	The functional hereditary units of protozoa.	Protozoan Genes,Gene, Protozoan,Protozoan Gene