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3bar

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[[Image:3bar.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP==
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|PDB= 3bar |SIZE=350|CAPTION= <scene name='initialview01'>3bar</scene>, resolution 1.90&Aring;
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<StructureSection load='3bar' size='340' side='right'caption='[[3bar]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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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>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=U5P:URIDINE-5&#39;-MONOPHOSPHATE'>U5P</scene>
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<table><tr><td colspan='2'>[[3bar]] is a 2 chain structure with sequence from [https://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=3BAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BAR FirstGlance]. <br>
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|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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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|GENE= ompdc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U5P:URIDINE-5-MONOPHOSPHATE'>U5P</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bar OCA], [https://pdbe.org/3bar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bar RCSB], [https://www.ebi.ac.uk/pdbsum/3bar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bar ProSAT]</span></td></tr>
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</table>
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'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase covalently modified by 6-azido-UMP'''
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== Function ==
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[https://www.uniprot.org/uniprot/Q8IJH3_PLAF7 Q8IJH3_PLAF7]
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ba/3bar_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bar ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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.
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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==About this Structure==
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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<ref>PMID:18189347</ref>
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3BAR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BAR OCA].
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==Reference==
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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]
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[[Category: Orotidine-5'-phosphate decarboxylase]]
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[[Category: Plasmodium falciparum]]
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[[Category: Single protein]]
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[[Category: Bello, A M.]]
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[[Category: Kotra, L P.]]
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[[Category: Lau, W.]]
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[[Category: Liu, Y.]]
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[[Category: Pai, E F.]]
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[[Category: Poduch, E.]]
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[[Category: U5P]]
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[[Category: 6-azido-ump]]
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[[Category: covalently]]
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[[Category: crystal structure]]
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[[Category: lyase]]
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[[Category: orotidine 5'-phosphate decarboxylase]]
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[[Category: plasmodium falciparum]]
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[[Category: pyrimidine biosynthesis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:58:56 2008''
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3bar" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Plasmodium falciparum 3D7]]
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[[Category: Bello AM]]
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[[Category: Kotra LP]]
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[[Category: Lau W]]
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[[Category: Liu Y]]
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[[Category: Pai EF]]
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[[Category: Poduch E]]

Current revision

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

PDB ID 3bar

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