View source for 1zw1


==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='1zw1' size='340' side='right'caption='[[1zw1]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zw1]] 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=1ZW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZW1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</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>, <scene name='pdbligand=TN5:2-(4-AMINO-2-CHLOROPHENOXY)-5-CHLOROPHENOL'>TN5</scene></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=1zw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zw1 OCA], [https://pdbe.org/1zw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zw1 RCSB], [https://www.ebi.ac.uk/pdbsum/1zw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zw1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9BH77_PLAFA Q9BH77_PLAFA] 
== 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/zw/1zw1_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/main_output.php?pdb_ID=1zw1 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1zw1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Anderson JW]]
[[Category: Fidock DA]]
[[Category: Freundlich JS]]
[[Category: Jacobs Jr WR]]
[[Category: Jacobus DP]]
[[Category: Kuo M]]
[[Category: Lucumi E]]
[[Category: Sacchettini JC]]
[[Category: Sarantakis D]]
[[Category: Schiehser GA]]
[[Category: Shieh HM]]
[[Category: Yu M]]