Comparative Genome Analysis of Plasmodium falciparum Triosephosphate Isomerase and Cytochrome Oxidase; Effect of Antimalarial Drugs on the Enzyme Stability

Background: Malaria is a major global public health challenge. Plasmodium falciparum happens to be the most virulent among the causative parasites of malaria. The development of drug resistance in Plasmodium falciparum strains has built up a great interest in the search for new antimalarial drugs and drug targets. As part of a program to develop metabolic enzymes as potential drug targets, the 3-dimensional structure of Plasmodium falciparum triosephosphate isomerase was determined. The focus on glycolytic and electron transport chain enzymes in the malaria parasite results from the observation that in the asexual stage of the parasite in the human red blood cells, the energy requirements of the organism are almost exclusively met by glycolysis and the electron transport chain enzyme of the parasite remains highly stable and resistant. Materials and Methods: The amino acid sequences of the experimental enzymes were mined from the NCBI database and sequence aligment between the triosephosphate isomerase and cytochrome oxidase of P. falciparum and their respective human orthologs were performed using the ClustalW sequence alignment software. The alignments were visualized using the Bioedit software which is a biological sequence alignment editor. The MEGA7 software was used to view and highlight the protein conserved domains and variable sites while the prediction of the protein domain was done using the PSIPRED. The amino acid composition graph of the P. falciparum enzymes was also plotted using specific functions on the MEGA7 software. Results: Here, we present a computational analysis of the amino acid composition of Plasmodium falciparum triosephosphate isomerase and cytochrome oxidase which are cytosolic and mitochondrial enzymes respectively. An alignment was also carried out with the human orthologs of each of the respective analysed parasite enzyme sequence. This comparison with the human enzymes was used to predict their functional similarity in respect to therapeutic drug design and the predicted potency of the drug for prophylaxis and disease treatment. Conclusions: Antimalarial drugs targeted at the Plasmodium falciparum triosephosphate isomerase tends to act faster compared to the mitochondrial cytochrome oxidase drug target counterparts. The initial takes advantage on the cytosolic instability of the disulfide bonds which has been analysed also to be of a very minute quantity in the enzymes.