1zxb
From Proteopedia
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| - | [[ | + | ==Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase. Part 1:4'-Substituted Triclosan Derivatives== |
| + | <StructureSection load='1zxb' size='340' side='right' caption='[[1zxb]], [[Resolution|resolution]] 2.68Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1zxb]] 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=1ZXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZXB 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>, <scene name='pdbligand=TN3:3-CHLORO-4-(4-CHLORO-2-HYDROXYPHENOXY)-N-METHYLBENZAMIDE'>TN3</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nhd|1nhd]], [[1nhg|1nhg]], [[1nhw|1nhw]], [[1nnu|1nnu]], [[1zw1|1zw1]], [[1zsn|1zsn]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PfENR ([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/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=1zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zxb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1zxb RCSB], [http://www.ebi.ac.uk/pdbsum/1zxb PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/1zxb_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A structure-based approach has been taken to develop 4'-substituted analogs of triclosan that target the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of these compounds exhibit nanomolar potency against purified PfENR enzyme and modest (2-10microM) potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite. X-ray crystal structures of nitro 29, aniline 30, methylamide 37, and urea 46 demonstrate the presence of hydrogen-bonding interactions with residues in the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular parasites. | ||
| - | + | Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 1: 4'-substituted triclosan derivatives.,Freundlich JS, Anderson JW, Sarantakis D, Shieh HM, Yu M, Valderramos JC, Lucumi E, Kuo M, Jacobs WR Jr, Fidock DA, Schiehser GA, Jacobus DP, Sacchettini JC Bioorg Med Chem Lett. 2005 Dec 1;15(23):5247-52. Epub 2005 Sep 29. PMID:16198563<ref>PMID:16198563</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
| - | [[Category: Anderson, J W | + | [[Category: Anderson, J W]] |
| - | [[Category: Fidock, D A | + | [[Category: Fidock, D A]] |
| - | [[Category: Freundlich, J S | + | [[Category: Freundlich, J S]] |
| - | [[Category: Jacobs, W R | + | [[Category: Jacobs, W R]] |
| - | [[Category: Jacobus, D P | + | [[Category: Jacobus, D P]] |
| - | [[Category: Kuo, M | + | [[Category: Kuo, M]] |
| - | [[Category: Lucumi, E | + | [[Category: Lucumi, E]] |
| - | [[Category: Sacchettini, J C | + | [[Category: Sacchettini, J C]] |
| - | [[Category: Sarantakis, D | + | [[Category: Sarantakis, D]] |
| - | [[Category: Schiehser, G A | + | [[Category: Schiehser, G A]] |
| - | [[Category: Shieh, H M | + | [[Category: Shieh, H M]] |
| - | [[Category: Yu, M | + | [[Category: Yu, M]] |
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 09:22, 8 January 2015
Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase. Part 1:4'-Substituted Triclosan Derivatives
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