U. SOUTHAMPTON (UK) — New research on vitamin B6 could lead to drugs that target the pathogen that causes malaria.
The University of Southampton research will enable scientists to learn more about the nature of the enzymes required for vitamin biosynthesis by the malaria-causing pathogen Plasmodium.
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.
Malaria leads 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 anti-malarial chemotherapeutics.
Using the University’s Southampton Diffraction Centre, researchers have now been able to describe the malarial enzymes responsible for Vitamin B6 biosynthesis with atomic 3D structures.
Vitamin B6 biosynthesis is a highly organized process involving an enzyme complex of 24 protein subunits. As reported in the journal Structure, the assembly from individual proteins was studied by electron microscopy in collaboration with the Boettcher group at the University of Edinburgh.
Ivo Tews, lecturer in structural biology and study author, says: “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 enzyme complex has a fascinating internal tunnel for the transfer of reactive reaction intermediates. The studies also discovered an unexpected organization of enzyme complexes into fibers.
“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.”
The research is a European Union F6 funded program.
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