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2q8z

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[[Image:2q8z.jpg|left|200px]]<br /><applet load="2q8z" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2q8z, resolution 1.80&Aring;" />
 
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'''Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-UMP'''<br />
 
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==Overview==
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==Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-UMP==
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<StructureSection load='2q8z' size='340' side='right'caption='[[2q8z]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2q8z]] 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=2Q8Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q8Z FirstGlance]. <br>
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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]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
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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=2q8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q8z OCA], [https://pdbe.org/2q8z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q8z RCSB], [https://www.ebi.ac.uk/pdbsum/2q8z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q8z ProSAT]</span></td></tr>
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</table>
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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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[[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/q8/2q8z_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=2q8z 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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2Q8Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum_dd2 Plasmodium falciparum dd2] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NUP:'>NUP</scene>, <scene name='pdbligand=7PE:'>7PE</scene> and <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q8Z OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=18189347 18189347]
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</div>
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[[Category: Plasmodium falciparum dd2]]
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<div class="pdbe-citations 2q8z" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Bello, A M.]]
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<references/>
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[[Category: Hui, R.]]
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__TOC__
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[[Category: Kotra, L P.]]
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</StructureSection>
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[[Category: Lau, W.]]
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[[Category: Large Structures]]
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[[Category: Liu, Y.]]
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[[Category: Plasmodium falciparum 3D7]]
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[[Category: Pai, E F.]]
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[[Category: Bello AM]]
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[[Category: 7PE]]
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[[Category: Hui R]]
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[[Category: NUP]]
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[[Category: Kotra LP]]
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[[Category: PEG]]
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[[Category: Lau W]]
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[[Category: SO4]]
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[[Category: Liu Y]]
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[[Category: 6-amino-ump]]
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[[Category: Pai EF]]
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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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:13 2008''
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Current revision

Crystal structure of Plasmodium falciparum orotidine 5'-phosphate decarboxylase complexed with 6-amino-UMP

PDB ID 2q8z

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