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New page: left|200px<br /><applet load="1t56" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t56, resolution 1.70Å" /> '''Crystal structure of...
 
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[[Image:1t56.gif|left|200px]]<br /><applet load="1t56" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1t56, resolution 1.70&Aring;" />
'''Crystal structure of TetR family repressor M. tuberculosis EthR'''<br />


==Overview==
==Crystal structure of TetR family repressor M. tuberculosis EthR==
Ethionamide has been used for more than 30 years as a second-line, chemotherapeutic to treat tuberculosis patients who have developed, resistance to first-line drugs, such as isoniazid (INH) and rifampicin., Activation of the pro-drug ethionamide is regulated by the Baeyer-Villiger, monooxygenase EthA and the TetR/CamR family repressor EthR, whose open, reading frames are separated by 75 bp on the Mycobacterium tuberculosis, genome. EthR has been shown to repress transcription of the activator gene, ethA by binding to this intergenic region, thus contributing to, ethionamide resistance. We have determined the crystal structure of EthR, to 1.7A resolution, revealing a dimeric two-domain molecule with an, overall architecture typical for TetR/CamR repressor proteins. A 20A long, hydrophobic tunnel-like cavity in the "drug-binding" domain of EthR is, occupied by two 1,4-dioxane molecules, a component of the crystallisation, buffer. Comparing the present structure to those of the homologues, Staphylococcus aureus QacR and Escherichia coli TetR leads to the, hypothesis that the hydrophobic cavity constitutes a binding site for an, as yet unknown ligand that might regulate DNA-binding of EthR.
<StructureSection load='1t56' size='340' side='right'caption='[[1t56]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1t56]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T56 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=1t56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t56 OCA], [https://pdbe.org/1t56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t56 RCSB], [https://www.ebi.ac.uk/pdbsum/1t56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t56 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>
== 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/t5/1t56_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=1t56 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1T56 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_h37rv Mycobacterium tuberculosis h37rv] with DIO and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1T56 OCA].
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
 
== References ==
==Reference==
<references/>
Crystal structure of the TetR/CamR family repressor Mycobacterium tuberculosis EthR implicated in ethionamide resistance., Dover LG, Corsino PE, Daniels IR, Cocklin SL, Tatituri V, Besra GS, Futterer K, J Mol Biol. 2004 Jul 23;340(5):1095-105. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15236969 15236969]
__TOC__
[[Category: Mycobacterium tuberculosis h37rv]]
</StructureSection>
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Besra, G.S.]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Cocklin, S.L.]]
[[Category: Besra GS]]
[[Category: Corsino, P.E.]]
[[Category: Cocklin SL]]
[[Category: Daniels, I.R.]]
[[Category: Corsino PE]]
[[Category: Dover, L.G.]]
[[Category: Daniels IR]]
[[Category: Futterer, K.]]
[[Category: Dover LG]]
[[Category: Tatituri, V.]]
[[Category: Futterer K]]
[[Category: DIO]]
[[Category: Tatituri V]]
[[Category: GOL]]
[[Category: dimer]]
[[Category: helix-turn-helix]]
[[Category: tetr family]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:39:49 2007''

Latest revision as of 08:36, 14 February 2024

Crystal structure of TetR family repressor M. tuberculosis EthR

1t56, resolution 1.70Å

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