1zsn: Difference between revisions

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OCA

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-[[Image:1zsn.gif|left|200px]]<br /><applet load="1zsn" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1zsn, resolution 2.992&Aring;" />
-'''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 />
-==Overview==
+==Synthesis, Biological Activity, and X-Ray Crystal Structural Analysis of Diaryl Ether Inhibitors of Malarial Enoyl ACP Reductase. Part 1:4'-Substituted Triclosan Derivatives==
-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.
+<StructureSection load='1zsn' size='340' side='right'caption='[[1zsn]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1zsn]] 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=1ZSN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZSN 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]] 2.992&#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=TN2:5-CHLORO-2-(2-CHLORO-4-NITROPHENOXY)PHENOL'>TN2</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=1zsn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zsn OCA], [https://pdbe.org/1zsn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zsn RCSB], [https://www.ebi.ac.uk/pdbsum/1zsn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zsn 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/zs/1zsn_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=1zsn 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.
-==About this Structure==
+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>
-ZSN 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=TN2:'>TN2</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=1ZSN OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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]
+</div>
-[[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
+<div class="pdbe-citations 1zsn" 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: Single protein]]
+[[Category: Anderson JW]]
-[[Category: Anderson, J.W.]]
+[[Category: Fidock DA]]
-[[Category: Fidock, D.A.]]
+[[Category: Freundlich JS]]
-[[Category: Freundlich, J.S.]]
+[[Category: Jacobs Jr WR]]
-[[Category: Jacobus, D.P.]]
+[[Category: Jacobus DP]]
-[[Category: Jr., W.R.Jacobs.]]
+[[Category: Kuo M]]
-[[Category: Kuo, M.]]
+[[Category: Lucumi E]]
-[[Category: Lucumi, E.]]
+[[Category: Sacchettini JC]]
-[[Category: Sacchettini, J.C.]]
+[[Category: Sarantakis D]]
-[[Category: Sarantakis, D.]]
+[[Category: Schiehser GA]]
-[[Category: Schiehser, G.A.]]
+[[Category: Shieh HM]]
-[[Category: Shieh, H.M.]]
+[[Category: Yu M]]
-[[Category: Yu, M.]]
-[[Category: NAD]]
-[[Category: TN2]]
-[[Category: oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:42:00 2008''