A new study has sorted out the nature of the enzymes needed for vitamin biosynthesis by the malaria causing pathogen Plasmodium. It could eventually lead to the design of more useful drugs to battle the disease.
Vitamins are essential nutrients required in small amounts, the lack of which leads to deficiencies.
Many pathogenic microorganisms produce vitamins, and these biosynthetic pathways may provide suitable targets for development of new drugs.
Indeed antifolates targeting vitamin B9 biosynthesis of the malarial parasites have been proven valuable chemotherapeutics for the treatment of malaria, one of the most devastating infectious diseases leading to nearly 250 million cases worldwide and about 1 million deaths annually.
Vitamin B6 biosynthesis of the parasite has been discussed as a drug novel target.
A major factor hindering malaria control is the high degree of resistance developed by Plasmodium species against currently available drugs. Hence, there is still an urgent need for the identification of novel drug targets as well as antimalarial chemotherapeutics.
Scientists at the University of Southampton have now been able to describe the malarial enzymes responsible for Vitamin B6 biosynthesis with atomic 3D structures.
Vitamin B6 biosynthesis 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.
"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," said Dr Ivo Tews, 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," Dr Tews added.
The research has been published in the latest issue of the journal, Structure.