2nq8: Difference between revisions
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==Malarial enoyl acyl ACP reductase bound with INH-NAD adduct== | ==Malarial enoyl acyl ACP reductase bound with INH-NAD adduct== | ||
<StructureSection load='2nq8' size='340' side='right' caption='[[2nq8]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2nq8' size='340' side='right' caption='[[2nq8]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE+DINUCLEOTIDE'>ZID</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZID:ISONICOTINIC-ACETYL-NICOTINAMIDE-ADENINE+DINUCLEOTIDE'>ZID</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 PLAFA])</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=2nq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nq8 OCA], [http://pdbe.org/2nq8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nq8 RCSB], [http://www.ebi.ac.uk/pdbsum/2nq8 PDBsum]</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=2nq8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nq8 OCA], [http://pdbe.org/2nq8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nq8 RCSB], [http://www.ebi.ac.uk/pdbsum/2nq8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nq8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nq/2nq8_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nq/2nq8_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 20:14, 15 August 2018
Malarial enoyl acyl ACP reductase bound with INH-NAD adductMalarial enoyl acyl ACP reductase bound with INH-NAD adduct
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe x-ray crystal structures of five triclosan analogs, in addition to that of the isoniazid-NAD adduct, are described in relation to their integral role in the design of potent inhibitors of the malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of the novel 5-substituted analogs exhibit low micromolar potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and inhibit purified PfENR enzyme with IC50 values of <200 nM. This study has significantly expanded the knowledge base with regard to the structure-activity relationship of triclosan while affording gains against cultured parasites and purified PfENR enzyme. In contrast to a recent report in the literature, these results demonstrate the ability to improve the in vitro potency of triclosan significantly by replacing the suboptimal 5-chloro group with larger hydrophobic moieties. The biological and x-ray crystallographic data thus demonstrate the flexibility of the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular Plasmodium parasites. X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy.,Freundlich JS, Wang F, Tsai HC, Kuo M, Shieh HM, Anderson JW, Nkrumah LJ, Valderramos JC, Yu M, Kumar TR, Valderramos SG, Jacobs WR Jr, Schiehser GA, Jacobus DP, Fidock DA, Sacchettini JC J Biol Chem. 2007 Aug 31;282(35):25436-44. Epub 2007 Jun 13. PMID:17567585[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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