1zxb

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[[Image:1zxb.gif|left|200px]]<br /><applet load="1zxb" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zxb, resolution 2.68&Aring;" />
 
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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'''<br />
 
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==Overview==
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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==
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<StructureSection load='1zxb' size='340' side='right'caption='[[1zxb]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zxb]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=1ZXB FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.68&#8491;</td></tr>
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<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>, <scene name='pdbligand=TN3:3-CHLORO-4-(4-CHLORO-2-HYDROXYPHENOXY)-N-METHYLBENZAMIDE'>TN3</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zxb OCA], [https://pdbe.org/1zxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zxb RCSB], [https://www.ebi.ac.uk/pdbsum/1zxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zxb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q9BH77_PLAFA Q9BH77_PLAFA]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/1zxb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/main_output.php?pdb_ID=1zxb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== 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.
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.
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==About this Structure==
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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>
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1ZXB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=TN3:'>TN3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZXB OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16198563 16198563]
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</div>
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[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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<div class="pdbe-citations 1zxb" style="background-color:#fffaf0;"></div>
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[[Category: Plasmodium falciparum]]
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[[Category: Single protein]]
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[[Category: Anderson, J W.]]
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[[Category: Fidock, D A.]]
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[[Category: Freundlich, J S.]]
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[[Category: Jacobus, D P.]]
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[[Category: Jr., W R.Jacobs.]]
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[[Category: Kuo, M.]]
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[[Category: Lucumi, E.]]
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[[Category: Sacchettini, J C.]]
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[[Category: Sarantakis, D.]]
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[[Category: Schiehser, G A.]]
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[[Category: Shieh, H M.]]
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[[Category: Yu, M.]]
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[[Category: NAD]]
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[[Category: TN3]]
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[[Category: oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:59 2008''
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==See Also==
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*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Plasmodium falciparum]]
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[[Category: Anderson JW]]
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[[Category: Fidock DA]]
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[[Category: Freundlich JS]]
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[[Category: Jacobs Jr WR]]
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[[Category: Jacobus DP]]
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[[Category: Kuo M]]
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[[Category: Lucumi E]]
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[[Category: Sacchettini JC]]
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[[Category: Sarantakis D]]
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[[Category: Schiehser GA]]
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[[Category: Shieh HM]]
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[[Category: Yu M]]

Current revision

Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase. Part 1:4'-Substituted Triclosan Derivatives

PDB ID 1zxb

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