2q8z
From Proteopedia
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|PDB= 2q8z |SIZE=350|CAPTION= <scene name='initialview01'>2q8z</scene>, resolution 1.80Å | |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> | |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= | + | |LIGAND= <scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=NUP:6-AMINOURIDINE+5'-MONOPHOSPHATE'>NUP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
| - | |GENE= PF10_0225 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | + | |GENE= PF10_0225 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 Plasmodium falciparum 3D7]) |
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2q8l|2Q8L]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8z OCA], [http://www.ebi.ac.uk/pdbsum/2q8z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q8z RCSB]</span> | ||
}} | }} | ||
| Line 16: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Q8Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ | + | 2Q8Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_3d7 Plasmodium falciparum 3d7]. 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://www.ncbi.nlm.nih.gov/pubmed/18189347 18189347] | 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 | + | [[Category: Plasmodium falciparum 3d7]] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bello, A M.]] | [[Category: Bello, A M.]] | ||
| Line 28: | Line 31: | ||
[[Category: Liu, Y.]] | [[Category: Liu, Y.]] | ||
[[Category: Pai, E F.]] | [[Category: Pai, E F.]] | ||
| - | [[Category: 7PE]] | ||
| - | [[Category: NUP]] | ||
| - | [[Category: PEG]] | ||
| - | [[Category: SO4]] | ||
[[Category: 6-amino-ump]] | [[Category: 6-amino-ump]] | ||
[[Category: lyase]] | [[Category: lyase]] | ||
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[[Category: plasmodium falciparum]] | [[Category: plasmodium falciparum]] | ||
| - | ''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 04:46:24 2008'' |
Revision as of 01:46, 31 March 2008
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , and | ||||||
| Ligands: | , , , | ||||||
| Gene: | PF10_0225 (Plasmodium falciparum 3D7) | ||||||
| Related: | 2Q8L
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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 3d7. 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
Page seeded by OCA on Mon Mar 31 04:46:24 2008
