2foi: Difference between revisions
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<StructureSection load='2foi' size='340' side='right'caption='[[2foi]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2foi' size='340' side='right'caption='[[2foi]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2foi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2foi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FOI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FOI FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JPA:4-(2,4-DICHLOROPHENOXY)-2-METHYLBIPHENYL-3-OL'>JPA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | |||
<tr id=' | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2foi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2foi OCA], [https://pdbe.org/2foi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2foi RCSB], [https://www.ebi.ac.uk/pdbsum/2foi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2foi ProSAT]</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=2foi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2foi OCA], [https://pdbe.org/2foi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2foi RCSB], [https://www.ebi.ac.uk/pdbsum/2foi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2foi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/C6KSZ2_PLAF7 C6KSZ2_PLAF7] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Anderson | [[Category: Anderson JW]] | ||
[[Category: Fidock | [[Category: Fidock DA]] | ||
[[Category: Freundlich | [[Category: Freundlich JS]] | ||
[[Category: Jacobs | [[Category: Jacobs Jr WR]] | ||
[[Category: Jacobus | [[Category: Jacobus DP]] | ||
[[Category: Karagyozov | [[Category: Karagyozov L]] | ||
[[Category: Kuo | [[Category: Kuo M]] | ||
[[Category: Lucumi | [[Category: Lucumi E]] | ||
[[Category: Sacchettini | [[Category: Sacchettini JC]] | ||
[[Category: Schiehser | [[Category: Schiehser GA]] | ||
[[Category: Shieh | [[Category: Shieh H]] | ||
[[Category: Tsai | [[Category: Tsai H]] | ||
[[Category: Valderramos | [[Category: Valderramos J]] | ||
[[Category: Yu | [[Category: Yu M]] | ||
Latest revision as of 12:30, 30 August 2023
Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase.Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase.
Structural highlights
FunctionEvolutionary 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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