2q8z: Difference between revisions
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[[Image:2q8z.jpg|left|200px]] | [[Image:2q8z.jpg|left|200px]] | ||
'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-UMP''' | {{Structure | ||
|PDB= 2q8z |SIZE=350|CAPTION= <scene name='initialview01'>2q8z</scene>, resolution 1.80Å | |||
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Residue+A+501'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Residue+B+501'>AC2</scene>, <scene name='pdbsite=AC3:Nup+Binding+Site+For+Residue+A+401'>AC3</scene>, <scene name='pdbsite=AC4:Nup+Binding+Site+For+Residue+B+401'>AC4</scene>, <scene name='pdbsite=AC5:7pe+Binding+Site+For+Residue+A+601'>AC5</scene>, <scene name='pdbsite=AC6:Peg+Binding+Site+For+Residue+A+701'>AC6</scene> and <scene name='pdbsite=AC7:Peg+Binding+Site+For+Residue+B+701'>AC7</scene> | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NUP:'>NUP</scene>, <scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene> and <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene> | |||
|ACTIVITY= | |||
|GENE= PF10_0225 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=57267 Plasmodium falciparum Dd2]) | |||
}} | |||
'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-UMP''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2Q8Z is a [ | 2Q8Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_dd2 Plasmodium falciparum dd2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8Z OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/18189347 18189347] | ||
[[Category: Plasmodium falciparum dd2]] | [[Category: Plasmodium falciparum dd2]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: plasmodium falciparum]] | [[Category: plasmodium falciparum]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:23:16 2008'' | ||
Revision as of 16:23, 20 March 2008
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| 2q8z, resolution 1.80Å | |||||||||||||
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| Sites: | AC1, AC2, AC3, AC4, AC5, AC6 and AC7 | ||||||||||||
| Ligands: | SO4, NUP, 7PE and PEG | ||||||||||||
| Gene: | PF10_0225 (Plasmodium falciparum Dd2) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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 dd2. 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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