Why vitamins could be key in fight against malaria
British and German researchers led by the University of Southampton in the United Kingdom have found that vitamins could help fight malaria. The findings of the study, presented in the journal Structure, could encourage the development of more effective drugs to fight this disease. This disorder affects more than 250 million people each year, and kills over 650 000 people. The study was funded in part by a grant under the EU's Sixth Framework Programme (FP6).
Vitamins are essential nutrients required only in small amounts. But a lack of even these small amounts leads to deficiencies. Researchers believe various pathogenic microorganisms produce vitamins; the biosynthetic pathways could be the key factor in getting novel therapies off the ground and running.
Studies have shown how antifolates targeting vitamin B9 biosynthesis of the malarial parasites play a vital role in the treatment of malaria. It should be noted that researchers have put the spotlight on vitamin B6 biosynthesis of the parasite as a drug novel target.
The World Health Organization (WHO) says early diagnosis and prompt treatment are two fundamental elements of malaria control. Both early and effective treatment of this disease can cut short the duration and extent of the infection.
But one of the biggest problems in trying to control malaria is the high degree of resistance developed by Plasmodium species against treatments being used today. Malaria is transmitted via the bites of infected mosquitoes. So finding novel drug targets and antimalarial chemotherapeutics is imperative.
In this study, the researchers identified the malarial enzymes responsible for vitamin B6 biosynthesis with atomic three-dimensional (3D) structures. The team points out that vitamin B6 biosynthesis is a very organised process that involves an enzyme complex of 24 protein subunits. Using electron microscopy, they probed the assembly from individual proteins.
'The structural studies explain how these vital enzymes are activated and show the substrate of vitamin B6 biosynthesis bound to give insights into the chemistry of PLP biosynthesis,' says Dr Ivo Tews, a lecturer in structural biology at the University of Southampton. 'The enzyme complex has a fascinating internal tunnel for the transfer of reactive reaction intermediates. The studies also discovered an unexpected organisation of enzyme complexes into fibres. The new data are a starting point for the development of specific inhibitors that target either the enzyme’s active sites or the assembly of the proteins into functional complexes.'
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