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3bar

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{{STRUCTURE_3bar| PDB=3bar | SCENE= }}
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'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP'''
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===Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 18189347 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18189347}}
==About this Structure==
==About this Structure==
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[[Category: Plasmodium falciparum]]
[[Category: Plasmodium falciparum]]
[[Category: Pyrimidine biosynthesis]]
[[Category: Pyrimidine biosynthesis]]
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Revision as of 03:56, 28 July 2008

Image:3bar.png

Template:STRUCTURE 3bar

Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP

Template:ABSTRACT PUBMED 18189347

About this Structure

3BAR is a Single protein structure of sequence from Plasmodium falciparum. 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 Feb 14;51(3):439-448. Epub 2008 Jan 12. PMID:18189347

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