View source for 1qvu


==Crystal structure of the multidrug binding transcriptional repressor QacR bound to two drugs: ethidium and proflavine==
<StructureSection load='1qvu' size='340' side='right'caption='[[1qvu]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1qvu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QVU 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]] 2.96&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ET:ETHIDIUM'>ET</scene>, <scene name='pdbligand=PRL:PROFLAVIN'>PRL</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=1qvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qvu OCA], [https://pdbe.org/1qvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qvu RCSB], [https://www.ebi.ac.uk/pdbsum/1qvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qvu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/QACR_STAAU QACR_STAAU] Transcriptional repressor of qacA. Binds to IR1, an unusually long 28 bp operator, which is located downstream from the qacA promoter and overlaps its transcription start site. QacR is induced from its IR1 site by binding to one of many structurally dissimilar cationic lipophilic compounds, which are also substrates of QacA.
== 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/qv/1qvu_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=1qvu ConSurf].
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== Publication Abstract from PubMed ==
The structural basis of simultaneous binding of two or more different drugs by any multidrug-binding protein is unknown and also how this can lead to a noncompetitive, uncompetitive or cooperative binding mechanism. Here, we describe the crystal structure of the Staphylococcus aureus multidrug-binding transcription repressor, QacR, bound simultaneously to ethidium (Et) and proflavin (Pf). The structure underscores the plasticity of the multidrug-binding pocket and reveals an alternative, Pf-induced binding mode for Et. To monitor the simultaneous binding of Pf and Et to QacR, as well as to determine the effects on the binding affinity of one drug when the other drug is prebound, a novel application of near-ultraviolet circular dichroism (UVCD) was developed. The UVCD equilibrium-binding studies revealed identical affinities of Pf for QacR in the presence or absence of Et, but significantly diminished affinity of Et for QacR when Pf is prebound, findings that are readily explicable by their structures. The principles for simultaneous binding of two different drugs discerned here are likely employed by the multidrug efflux transporters.

Structural mechanism of the simultaneous binding of two drugs to a multidrug-binding protein.,Schumacher MA, Miller MC, Brennan RG EMBO J. 2004 Aug 4;23(15):2923-30. Epub 2004 Jul 15. PMID:15257299<ref>PMID:15257299</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1qvu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus]]
[[Category: Brennan RG]]
[[Category: Miller MC]]
[[Category: Schumacher MA]]