3bar
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(New page: 200px<br /><applet load="3bar" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bar, resolution 1.90Å" /> '''Crystal structure of...)
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Revision as of 09:03, 31 January 2008
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Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP
Overview
Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug, resistance. In Plasmodia, orotidine 5'-monophosphate decarboxylase, (ODCase) is an essential enzyme for the de novo synthesis of uridine, 5'-monophosphate. Impairing ODCase in these pathogens is a promising, strategy to develop novel classes of therapeutics. Encouraged by our, recent discovery that 6-iodo uridine is a potent inhibitor of P., falciparum, we investigated the structure-activity relationships of, various C6 derivatives of UMP. 6-Cyano, 6-azido, 6-amino, 6-methyl, 6-, N-methylamino, and 6- N, N-dimethylamino derivatives of uridine were, evaluated against P. falciparum. The mononucleotides of 6-cyano, 6-azido, 6-amino, and 6-methyl uridine derivatives were studied as inhibitors of, plasmodial ODCase. 6-Azidouridine 5'-monophosphate is a potent covalent, inhibitor of P. falciparum ODCase. 6-Methyluridine exhibited weak, antimalarial activity against P. falciparum 3D7 isolate. 6- N-Methylamino, and 6- N, N-dimethylamino uridine derivatives exhibited moderate, antimalarial activities.
About this Structure
3BAR is a Single protein structure of sequence from Plasmodium falciparum with as ligand. Active as Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Structure-Activity Relationships of C6-Uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase., Bello AM, Poduch E, Liu Y, Wei L, Crandall I, Wang X, Dyanand C, Kain KC, Pai EF, Kotra LP, J Med Chem. 2008 Jan 12;. PMID:18189347
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