View source for 2uxu


==TtgR in complex with Naringenin==
<StructureSection load='2uxu' size='340' side='right'caption='[[2uxu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uxu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_putida Pseudomonas putida]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UXU 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAR:NARINGENIN'>NAR</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=2uxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uxu OCA], [https://pdbe.org/2uxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uxu RCSB], [https://www.ebi.ac.uk/pdbsum/2uxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uxu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TTGR_PSEPT TTGR_PSEPT] Represses expression from the ttgABC operon promoter and its own expression. Binds to a promoter region between the divergently transcribed ttgR and ttgABC genes/operons; in the presence of chloramphenicol or tetracycline this binding no longer occurs and ttgR and ttgABC are derepressed. This suggests that TtgR binds these antibiotics.<ref>PMID:11251828</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/ux/2uxu_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=2uxu ConSurf].
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== Publication Abstract from PubMed ==
Antibiotic resistance is a widely spread phenomenon. One major mechanism that underlies antibiotic resistance in bacteria is the active extrusion of toxic compounds through the membrane-bound efflux pumps that are often regulated at the transcriptional level. TtgR represses the transcription of TtgABC, a key efflux pump in Pseudomonas putida, which is highly resistant to antibiotics, solvents and toxic plant secondary products. Previously we showed that TtgR is the only reported repressor that binds to different classes of natural antimicrobial compounds, which are also extruded by the efflux pump. We report here five high-resolution crystal structures of TtgR from the solvent-tolerant strain DOT-T1E, including TtgR in complex with common antibiotics and plant secondary metabolites. We provide structural basis for the unique ligand binding properties of TtgR. We identify two distinct and overlapping ligand binding sites; the first one is broader and consists of mainly hydrophobic residues, whereas the second one is deeper and contains more polar residues including Arg176, a unique residue present in the DOT-T1E strain but not in other Pseudomonas strains. Phloretin, a plant antimicrobial, can bind to both binding sites with distinct binding affinities and stoichiometries. Results on ligand binding properties of native and mutant TtgR proteins using isothermal titration calorimetry confirm the binding affinities and stoichiometries, and suggest a potential positive cooperativity between the two binding sites. The importance of Arg176 in phloretin binding was further confirmed by the reduced ability of phloretin in releasing the mutant TtgR from bound DNA compared to the native protein. The results presented here highlight the importance and versatility of regulatory systems in bacterial antibiotic resistance and open up new avenues for novel antimicrobial development.

Crystal structures of multidrug binding protein TtgR in complex with antibiotics and plant antimicrobials.,Alguel Y, Meng C, Teran W, Krell T, Ramos JL, Gallegos MT, Zhang X J Mol Biol. 2007 Jun 8;369(3):829-40. Epub 2007 Mar 30. PMID:17466326<ref>PMID:17466326</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 2uxu" 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: Pseudomonas putida]]
[[Category: Alguel Y]]
[[Category: Gallegos M-T]]
[[Category: Krell T]]
[[Category: Meng C]]
[[Category: Ramos JL]]
[[Category: Teran W]]
[[Category: Zhang X]]