Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orotidine 5'-monophosphate (OMP) decarboxylase (OMPDC; EC 4.1.1.23) catalyzes the final step in the de novo synthesis of uridine 5'-monophosphate (UMP) and defects in the enzyme are lethal in the malaria parasite Plasmodium falciparum. Active recombinant P. falciparum OMPDC (PfOMPDC) was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 A resolution at 100 K using synchrotron radiation at the Swiss Light Source. The crystal exhibits trigonal symmetry (space group R3), with hexagonal unit-cell parameters a = b = 201.81, c = 44.03 A. With a dimer in the asymmetric unit, the solvent content is 46% (V(M) = 2.3 A3 Da(-1)).
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PMID:Crystallization and preliminary crystallographic analysis of orotidine 5'-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum. 1675 76

ODCase is a highly proficient enzyme responsible for the decarboxylation of orotidine monophosphate to generate uridine monophosphate. ODCase has attracted early attention due to its interesting mechanism of catalysis. In order to exploit therapeutic advantages due to the inhibition of ODCase, one must have selective inhibitors of this enzyme from the pathogen, or a dysregulated molecular mechanism involving ODCase. ODCase inhibitors have potential applications as anticancer agents, antiviral agents, antimalarial agents and potentially act against other parasitic diseases. A variety of C6-substituted uridine monophosphate derivatives have shown excellent inhibition of ODCase. 6-iodouridine is a potent inhibitor of the malaria parasite, and its monophosphate form covalently inhibits ODCase. A variety of inhibitors of ODCase with potential applications as therapeutic agents are discussed in this review.
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PMID:Design of inhibitors of ODCase. 2446 42