3bar
From Proteopedia
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|SITE= <scene name='pdbsite=AC1:U5p+Binding+Site+For+Residue+A+3000'>AC1</scene> and <scene name='pdbsite=AC2:U5p+Binding+Site+For+Residue+B+3000'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:U5p+Binding+Site+For+Residue+A+3000'>AC1</scene> and <scene name='pdbsite=AC2:U5p+Binding+Site+For+Residue+B+3000'>AC2</scene> | ||
|LIGAND= <scene name='pdbligand=U5P:URIDINE-5'-MONOPHOSPHATE'>U5P</scene> | |LIGAND= <scene name='pdbligand=U5P:URIDINE-5'-MONOPHOSPHATE'>U5P</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Orotidine-5'-phosphate_decarboxylase Orotidine-5'-phosphate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.23 4.1.1.23] </span> |
|GENE= ompdc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum]) | |GENE= ompdc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2q8l|2Q8L]], [[2q8z|2Q8Z]], [[2qaf|2QAF]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bar OCA], [http://www.ebi.ac.uk/pdbsum/3bar PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bar RCSB]</span> | ||
}} | }} | ||
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[[Category: Pai, E F.]] | [[Category: Pai, E F.]] | ||
[[Category: Poduch, E.]] | [[Category: Poduch, E.]] | ||
| - | [[Category: U5P]] | ||
[[Category: 6-azido-ump]] | [[Category: 6-azido-ump]] | ||
[[Category: covalently]] | [[Category: covalently]] | ||
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[[Category: pyrimidine biosynthesis]] | [[Category: pyrimidine biosynthesis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:24:39 2008'' |
Revision as of 02:24, 31 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | |||||||
| Gene: | ompdc (Plasmodium falciparum) | ||||||
| Activity: | Orotidine-5'-phosphate decarboxylase, with EC number 4.1.1.23 | ||||||
| Related: | 2Q8L, 2Q8Z, 2QAF
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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