3fng: Difference between revisions

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-[[Image:3fng.png|left|200px]]
-{{STRUCTURE_3fng|  PDB=3fng  |  SCENE=  }}
+==Crystal structure of InhA bound to triclosan derivative==
+<StructureSection load='3fng' size='340' side='right'caption='[[3fng]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3fng]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FNG 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]] 1.97&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JPL:5-(CYCLOHEXYLMETHYL)-2-(2,4-DICHLOROPHENOXY)PHENOL'>JPL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=3fng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fng OCA], [https://pdbe.org/3fng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fng RCSB], [https://www.ebi.ac.uk/pdbsum/3fng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fng ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]
+== 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/fn/3fng_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=3fng ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Triclosan has been previously shown to inhibit InhA, an essential enoyl acyl carrier protein reductase involved in mycolic acid biosynthesis, the inhibition of which leads to the lysis of Mycobacterium tuberculosis. Using a structure-based drug design approach, a series of 5-substituted triclosan derivatives was developed. Two groups of derivatives with alkyl and aryl substituents, respectively, were identified with dramatically enhanced potency against purified InhA. The most efficacious inhibitor displayed an IC(50) value of 21 nM, which was 50-fold more potent than triclosan. X-ray crystal structures of InhA in complex with four triclosan derivatives revealed the structural basis for the inhibitory activity. Six selected triclosan derivatives were tested against isoniazid-sensitive and resistant strains of M. tuberculosis. Among those, the best inhibitor had an MIC value of 4.7 mug mL(-1) (13 muM), which represents a tenfold improvement over the bacteriocidal activity of triclosan. A subset of these triclosan analogues was more potent than isoniazid against two isoniazid-resistant M. tuberculosis strains, demonstrating the significant potential for structure-based design in the development of next generation antitubercular drugs.
-===Crystal structure of InhA bound to triclosan derivative===
+Triclosan Derivatives: Towards Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.,Freundlich JS, Wang F, Vilcheze C, Gulten G, Langley R, Schiehser GA, Jacobus DP, Jacobs WR Jr, Sacchettini JC ChemMedChem. 2009 Jan 7. PMID:19130456<ref>PMID:19130456</ref>
-{{ABSTRACT_PUBMED_19130456}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3fng" style="background-color:#fffaf0;"></div>
-[[3fng]] is a 1 chain structure of [[Enoyl-Acyl-Carrier Protein Reductase]] with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FNG OCA].
 ==See Also==
-*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]]
+*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:019130456</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mycobacterium tuberculosis]]
-[[Category: Wang, F.]]
+[[Category: Wang F]]
-[[Category: Antibiotic resistance]]
-[[Category: Fatty acid biosynthesis]]
-[[Category: Inha]]
-[[Category: Lipid synthesis]]
-[[Category: Nad]]
-[[Category: Oxidoreductase]]
-[[Category: Triclosan]]
-[[Category: Tuberculosis]]