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Pv-MEDCPS (Pv089580): Plasmodium vivax 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
PDB Code 3B6N Target Class Malaria Target Pv-MECPS Alias n/a Disease Area/Function parasitic disease Date Deposited Oct 29 2007 Authors
About this structure
Isoprenoids are the oldest known biomolecules and the largest group of natural products. All 30,000 plus compounds are derived from merging isopentenyl pyrophosphate (IPP) and its isomer dimethylallyl pyrophosphate (DMAPP), adding extending the molecule one IPP unit at a time. There are two known distinct pathways for isoprenoid biosynthesis: the mevalonic acid-independent pathway for higher order eukaryotes and the non-mevalonate pathway (or MEP) for prokaryotes and protozoan eukaryotes.Plasmodium parasites have been confirmed to undergo the MEP pathway, which involves seven enzymes in biosynthesis of IPP. The fifth enzyme in this complex system is 2C-Methyl-D-erythritol-2,4-cyclophosphate synthase (MECDPS) which is responsible for the cyclization of 4-diphosphocytidyl-2C-methyl-D-erythritol to 2C-methyl-D-erythritol-2,4-cyclodiphosphate. Previous reports indicate that this enzyme may be the target of fosmidomycin which has been found to effectively inhibit the growth of multidrug resistant strains of Plasmodium parasites.
Our structure of PLasmodium vivax MEDCPS features Zn2+ in the active site, although magnesium and manganese have been seen in homologous structures.
