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| | ==Toxoplasma gondii Enoyl acyl carrier protein reductase== | | ==Toxoplasma gondii Enoyl acyl carrier protein reductase== |
| - | <StructureSection load='4o1m' size='340' side='right' caption='[[4o1m]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4o1m' size='340' side='right'caption='[[4o1m]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o1m]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O1M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o1m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O1M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o2s|2o2s]], [[3nj8|3nj8]], [[2ptg|2ptg]], [[2o2y|2o2y]], [[2o50|2o50]]</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=4o1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1m OCA], [https://pdbe.org/4o1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o1m RCSB], [https://www.ebi.ac.uk/pdbsum/4o1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1m ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Enoyl reductase, ENR, TGVEG_000410 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5811 TOXGO])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=4o1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1m OCA], [http://pdbe.org/4o1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o1m RCSB], [http://www.ebi.ac.uk/pdbsum/4o1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1m ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6UCJ9_TOXGO Q6UCJ9_TOXGO] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Toxgo]] | + | [[Category: Large Structures]] |
| - | [[Category: Muench, S P]] | + | [[Category: Toxoplasma gondii]] |
| - | [[Category: Prigge, S T]] | + | [[Category: Muench SP]] |
| - | [[Category: Rice, D W]] | + | [[Category: Prigge ST]] |
| - | [[Category: Wilkinson, C]] | + | [[Category: Rice DW]] |
| - | [[Category: Enoyl acyl carrier protein reductase]] | + | [[Category: Wilkinson C]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
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| Structural highlights
Function
Q6UCJ9_TOXGO
Publication Abstract from PubMed
The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1muM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.
The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target.,Wilkinson C, McPhillie MJ, Zhou Y, Woods S, Afanador GA, Rawson S, Khaliq F, Prigge ST, Roberts CW, Rice DW, McLeod R, Fishwick CW, Muench SP Bioorg Med Chem Lett. 2014 Feb 1;24(3):911-6. doi: 10.1016/j.bmcl.2013.12.066., Epub 2013 Dec 22. PMID:24398298[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wilkinson C, McPhillie MJ, Zhou Y, Woods S, Afanador GA, Rawson S, Khaliq F, Prigge ST, Roberts CW, Rice DW, McLeod R, Fishwick CW, Muench SP. The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target. Bioorg Med Chem Lett. 2014 Feb 1;24(3):911-6. doi: 10.1016/j.bmcl.2013.12.066., Epub 2013 Dec 22. PMID:24398298 doi:http://dx.doi.org/10.1016/j.bmcl.2013.12.066
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