4dw6: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dw6]] 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=4DW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DW6 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dw6]] 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=4DW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DW6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MN:N-[4-(1,3-BENZOTHIAZOL-2-YL)PHENYL]-2-(3-METHOXYPHENOXY)ACETAMIDE'>0MN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene></td></tr>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MN:N-[4-(1,3-BENZOTHIAZOL-2-YL)PHENYL]-2-(3-METHOXYPHENOXY)ACETAMIDE'>0MN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</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=4dw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dw6 OCA], [https://pdbe.org/4dw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dw6 RCSB], [https://www.ebi.ac.uk/pdbsum/4dw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dw6 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=4dw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dw6 OCA], [https://pdbe.org/4dw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dw6 RCSB], [https://www.ebi.ac.uk/pdbsum/4dw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dw6 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/ETHR_MYCTU ETHR_MYCTU]] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).<ref>PMID:10869356</ref> <ref>PMID:10944230</ref>
[https://www.uniprot.org/uniprot/ETHR_MYCTU ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).<ref>PMID:10869356</ref> <ref>PMID:10944230</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In this paper, we describe the screening of a 14640-compound library using a novel whole mycobacteria phenotypic assay to discover inhibitors of EthR, a transcriptional repressor implicated in the innate resistance of Mycobacterium tuberculosis to the second-line antituberculosis drug ethionamide. From this screening a new chemical family of EthR inhibitors bearing an N-phenylphenoxyacetamide motif was identified. The X-ray structure of the most potent compound crystallized with EthR inspired the synthesis of a 960-member focused library. These compounds were tested in vitro using a rapid thermal shift assay on EthR to accelerate the optimization. The best compounds were synthesized on a larger scale and confirmed as potent ethionamide boosters on M. tuberculosis -infected macrophages. Finally, the cocrystallization of the best optimized analogue with EthR revealed an unexpected reorientation of the ligand in the binding pocket.
 
Discovery of novel N-phenylphenoxyacetamide derivatives as EthR inhibitors and ethionamide boosters by combining high-throughput screening and synthesis.,Flipo M, Willand N, Lecat-Guillet N, Hounsou C, Desroses M, Leroux F, Lens Z, Villeret V, Wohlkonig A, Wintjens R, Christophe T, Kyoung Jeon H, Locht C, Brodin P, Baulard AR, Deprez B J Med Chem. 2012 Jul 26;55(14):6391-402. Epub 2012 Jul 17. PMID:22738293<ref>PMID:22738293</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dw6" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Retrieved from "https://proteopedia.org/4dw6"