Characterization of Dihydroorotate Dehydrogenase for Malaria Therapy: Production,purification and Co-crystallization of Plasmodium Falciparum and Plasmodium Vivax Dhodh with Novel Inhibitors

Malaria remains a world's disease burden causing high incidences of mortality in susceptible populations. Severe cases of malaria are caused by parasites of the apicomplexan Plasmodium falciparum localized in sub-saharan Africa whereas less severe malaria but most prevalent outside Africa is caused by Plasmodium vivax. Malaria campaigns through vector control and effective artemesinins-based combination therapy has considerably reduced malarial mortality ratesin the past decade. However, increasing cases of drug resistance has raised an urgent need for development of new anti-malarial drugs. In-silico drug design using the structure of the biological target is the latest lead optimization option in search of more potent drugs. In this work, i sought to determine the 3-dimensional structure of the biological target,dehydroorotate dihydrogenase(DHODH) from the above mentioned plasmodia species co-crystallized with novel drug candidates. Characterization of the parasitic DHODH involved target gene cloning,site directed mutagenesis,protein expression and purification and subsequent co-crystallization for structure determination. This book therefore,targets life science research professionals