3vi2
From Proteopedia
(Difference between revisions)
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| - | + | ==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=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3vi2]] is a 2 chain structure with 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=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> | ||
| + | </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> | ||
| + | <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 Plasmodium falciparum])</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'>[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://www.rcsb.org/pdb/explore.do?structureId=3vi2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vi2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Orotidine-5'-phosphate decarboxylase]] | [[Category: Orotidine-5'-phosphate decarboxylase]] | ||
[[Category: Plasmodium falciparum]] | [[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, S R]] |
| - | [[Category: Matsumura, H | + | [[Category: Matsumura, H]] |
| - | [[Category: Mizohata, E | + | [[Category: Mizohata, E]] |
| - | [[Category: Takashima, Y | + | [[Category: Takashima, Y]] |
[[Category: Lyase-lyase inhibitor complex]] | [[Category: Lyase-lyase inhibitor complex]] | ||
[[Category: Orotidine 5 f-monophosphate decarboxylase]] | [[Category: Orotidine 5 f-monophosphate decarboxylase]] | ||
Revision as of 07:20, 21 December 2014
Crystal Structure Analysis of Plasmodium falciparum OMP Decarboxylase in complex with inhibitor HMOA
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