2q8z | pdb_00002q8z
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Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-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
2Q8Z is a Single protein structure of sequence from Plasmodium falciparum 3d7 with SO4, NUP, 7PE and PEG as ligands. Known structural/functional Sites: AC1, AC2, AC3, AC4, AC5, AC6 and AC7. 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
Page seeded by OCA on Thu Jan 31 10:58:55 2008
