Dihydroorotate dehydrogenase from the Phytopathogenic Oomycete Phytophthora infestans as a novel target for crop control
Author: Garavito Diago, Manuel Fernando
Publication date: 2010
Content type: masterThesis
The oomycete Phytophthora infestans (Mont.) de Bary, the causal agent of the tomato and potato late blight, causes tremendous crop and economic losses worldwide. In Colombia this pathogen is currently a devastating risk for the highlands dedicated to production of potato and tomato, hosts of this oomycete. Yet, current control strategies are far from being adequate and new ones are urgently needed. An interesting and unexplored alternative to control human parasites based on the inhibition of the de novo pyrimidine biosynthetic pathway might work as well in P. infestans. In this study we investigated the pathogen's dihydroorotase dehydrogenase DHODase, which catalyzes the fourth and only redox step of the pathway as a target to develop control strategies. We propose that this enzyme is member of the DHODase family 2, which compromises a mitochondrial bound enzyme with quinones as direct electron acceptors. In silico, preliminary molecular docking assays using homology modeled structures reveal that key structural aspects of the enzyme such as its apparent binding site flexibility could be exploited to develop species-selective inhibitors. A full length and an N-terminally truncated DHODase were expressed as recombinant proteins and complemented a DHODase-deficient bacterial host.
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