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| | ==Crystal Structure Analysis of Plasmodium falciparum OMP Decarboxylase in complex with inhibitor HMOA== | | ==Crystal Structure Analysis of Plasmodium falciparum OMP Decarboxylase in complex with inhibitor HMOA== |
| - | <StructureSection load='3vi2' size='340' side='right' caption='[[3vi2]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3vi2' size='340' side='right'caption='[[3vi2]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vi2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VI2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VI2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vi2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VI2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HMZ:4-(2-HYDROXY-4-METHOXYPHENYL)-4-OXOBUTANOIC+ACID'>HMZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ompdc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HMZ:4-(2-HYDROXY-4-METHOXYPHENYL)-4-OXOBUTANOIC+ACID'>HMZ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vi2 OCA], [https://pdbe.org/3vi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vi2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vi2 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vi2 OCA], [http://pdbe.org/3vi2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vi2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vi2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vi2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q8T6J6_PLAFA Q8T6J6_PLAFA] |
| - | Orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum (PfOMPDC) catalyses the final step in the de novo synthesis of uridine 5'-monophosphate (UMP) from orotidine 5'-monophosphate (OMP). A defective PfOMPDC enzyme is lethal to the parasite. Novel in silico screening methods were performed to select 14 inhibitors against PfOMPDC, with a high hit rate of 9%. X-ray structure analysis of PfOMPDC in complex with one of the inhibitors, 4-(2-hydroxy-4-methoxyphenyl)-4-oxobutanoic acid, was carried out to at 2.1 A resolution. The crystal structure revealed that the inhibitor molecule occupied a part of the active site that overlaps with the phosphate-binding region in the OMP- or UMP-bound complexes. Space occupied by the pyrimidine and ribose rings of OMP or UMP was not occupied by this inhibitor. The carboxyl group of the inhibitor caused a dramatic movement of the L1 and L2 loops that play a role in the recognition of the substrate and product molecules. Combining part of the inhibitor molecule with moieties of the pyrimidine and ribose rings of OMP and UMP represents a suitable avenue for further development of anti-malarial drugs.
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| - | The in silico screening and X-ray structure analysis of the inhibitor complex of Plasmodium falciparum orotidine 5'-monophosphate decarboxylase.,Takashima Y, Mizohata E, Krungkrai SR, Fukunishi Y, Kinoshita T, Sakata T, Matsumura H, Krungkrai J, Horii T, Inoue T J Biochem. 2012 Aug;152(2):133-138. Epub 2012 Jun 26. PMID:22740703<ref>PMID:22740703</ref>
| + | ==See Also== |
| - | | + | *[[Uridine 5'-monophosphate synthase 3D structures|Uridine 5'-monophosphate synthase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3vi2" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Orotidine-5'-phosphate decarboxylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Plafa]] | + | [[Category: Plasmodium falciparum]] |
| - | [[Category: Horii, T]] | + | [[Category: Horii T]] |
| - | [[Category: Inoue, T]] | + | [[Category: Inoue T]] |
| - | [[Category: Krungkrai, J]] | + | [[Category: Krungkrai J]] |
| - | [[Category: Krungkrai, S R]] | + | [[Category: Krungkrai SR]] |
| - | [[Category: Matsumura, H]] | + | [[Category: Matsumura H]] |
| - | [[Category: Mizohata, E]] | + | [[Category: Mizohata E]] |
| - | [[Category: Takashima, Y]] | + | [[Category: Takashima Y]] |
| - | [[Category: Lyase-lyase inhibitor complex]]
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| - | [[Category: Orotidine 5 f-monophosphate decarboxylase]]
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