3g1m

<StructureSection load='3g1m' size='340' side='right' caption='[[3g1m]], [[Resolution|resolution]] 1.70&Aring;' scene=''>

<table><tr><td colspan='2'>[[3g1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3G1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3G1M FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RF3:1-(THIOPHEN-2-YLACETYL)-4-(3-THIOPHEN-2-YL-1,2,4-OXADIAZOL-5-YL)PIPERIDINE'>RF3</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u9n|1u9n]], [[1u9o|1u9o]], [[3g1l|3g1l]], [[3g1o|3g1o]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ethR, MT3970, Rv3855 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3g1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3g1m OCA], [http://pdbe.org/3g1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3g1m RCSB], [http://www.ebi.ac.uk/pdbsum/3g1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3g1m ProSAT]</span></td></tr>

[[http://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>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g1/3g1m_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

The side effects associated with tuberculosis therapy bring with them the risk of noncompliance and subsequent drug resistance. Increasing the therapeutic index of antituberculosis drugs should thus improve treatment effectiveness. Several antituberculosis compounds require in situ metabolic activation to become inhibitory. Various thiocarbamide-containing drugs, including ethionamide, are activated by the mycobacterial monooxygenase EthA, the production of which is controlled by the transcriptional repressor EthR. Here we identify drug-like inhibitors of EthR that boost the bioactivation of ethionamide. Compounds designed and screened for their capacity to inhibit EthR-DNA interaction were co-crystallized with EthR. We exploited the three-dimensional structures of the complexes for the synthesis of improved analogs that boosted the ethionamide potency in culture more than tenfold. In Mycobacterium tuberculosis-infected mice, one of these analogs, BDM31343, enabled a substantially reduced dose of ethionamide to lessen the mycobacterial load as efficiently as the conventional higher-dose treatment. This provides proof of concept that inhibiting EthR improves the therapeutic index of thiocarbamide derivatives, which should prompt reconsideration of their use as first-line drugs.

 

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[[Category: Aumercier, M]]

[[Category: Baulard, A R]]

[[Category: Bifani, P]]

[[Category: Carette, X]]

[[Category: Delcroix, G]]

[[Category: Deprez, B]]

[[Category: Deprez-Poulain, R]]

[[Category: Desroses, M]]

[[Category: Dirie, B]]

[[Category: Frenois, F]]

[[Category: Leroux, F]]

[[Category: Locht, C]]

[[Category: Mathys, V]]

[[Category: Singhal, A]]

[[Category: Villeret, V]]

[[Category: Willand, N]]

[[Category: Willery, E]]

[[Category: Transcription regulation]]