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Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic potential
M E Meza-Avina1, L Wei, M G Buhendwa
1Center for Molecular Design and Preformulations, Toronto General Hopsital, Toronto, Ontario, Canada M5G 2C4, Canada.
Abstract:
Orotidine 5'-monophosphate decarboxylase (ODCase) is among the most proficient enzymes, and catalyzes the decarboxylation of OMP to UMP. An overview of ODCase and various proposals for its catalytic mechanism of decarboxylation are briefly presented here. A number of inhibitors of ODCase and new developments in the X-ray structures of ODCases from different species are discussed in the context of their therapeutic potential against cancer and infectious diseases. Latest discoveries in the inhibition of ODCase, for example using the novel C6 substitutions on the uridine, open new doors for drug discovery targeting parasitic diseases such as malaria.
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