View source for 5nj0


==EthR complex==
<StructureSection load='5nj0' size='340' side='right'caption='[[5nj0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nj0]] 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=5NJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NJ0 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8YW:~{N}-[(2~{R})-2-(4-nitrophenyl)-2-oxidanyl-ethyl]-1,3-benzodioxole-5-carboxamide'>8YW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5nj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nj0 OCA], [https://pdbe.org/5nj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nj0 RCSB], [https://www.ebi.ac.uk/pdbsum/5nj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nj0 ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The transcriptional repressor EthR from Mycobacterium tuberculosis, a member of the TetR family of prokaryotic homo-dimeric transcription factors, controls the expression of the mycobacterial mono-oxygenase EthA. EthA is responsible for the bio-activation of the second-line tuberculosis pro-drug ethionamide, and consequently EthR inhibitors boost drug efficacy. Here, we present a comprehensive in silico structure-based screening protocol that led to the identification of a number of novel scaffolds of EthR inhibitors in subsequent biophysical screening by thermal shift assay. Growth inhibition assays demonstrated that five of the twenty biophysical hits were capable of boosting ethionamide activity in vitro, with the best novel scaffold displaying an EC50 of 34 muM. In addition, the co-crystal structures of EthR with four new ligands at resolution ranging from 2.1 to 1.4 A confirm the binding and inactivation mode, and will enable future lead development.

New active leads for tuberculosis booster drugs by structure-based drug discovery.,Tatum NJ, Liebeschuetz JW, Cole JC, Frita R, Herledan A, Baulard AR, Willand N, Pohl E Org Biomol Chem. 2017 Nov 28. doi: 10.1039/c7ob00910k. PMID:29182187<ref>PMID:29182187</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nj0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Baulard AR]]
[[Category: Cole JC]]
[[Category: Pohl E]]
[[Category: Tatum NJ]]