Vitamin research could lead to new malaria drugs

University of Southampton team investigate Vitamin B6 biosynthesis of the Plasmodium parasite

Dr Ivo Tews at the Rigaku imager for crystallisation plates

Research on vitamins by a team at the University of Southampton could lead to novel drugs to treat malaria.

The study will enable scientists to learn more about the nature of the enzymes required for vitamin biosynthesis by the malaria-causing pathogen Plasmodium. Many pathogenic microorganisms produce vitamins, and these biosynthetic pathways may provide suitable targets for the development of new drugs.

Antifolates targeting vitamin B9 biosynthesis of the malarial parasites have already been proven valuable chemotherapeutics for the treatment of malaria, which causes around one million deaths each year. Vitamin B6 biosynthesis of the parasite has also been discussed as a drug novel target.

Using the Southampton Diffraction Centre, researchers have been able to describe the malarial enzymes responsible for Vitamin B6 biosynthesis with atomic 3D structures. This is a highly organised process involving an enzyme complex of 24 protein subunits. The assembly from individual proteins was studied by electron microscopy in collaboration with the Boettcher group at the University of Edinburgh.

Dr Ivo Tews, lecturer in Structural Biology at the University of Southampton, said: ‘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. The studies also discovered an unexpected organisation of enzyme complexes into fibres.’

The research paper, Assembly of the eukaryotic PLP-synthase complex from Plasmodium and activation of the Pdx1 enzyme, which is an EU F6 funded programme for two years, is published in the latest issue of the journal, Structure.

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