3f8c: Difference between revisions
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==Crystal structure of multidrug binding transcriptional regulator LmrR complexed with Hoechst 33342== | |||
=== | <StructureSection load='3f8c' size='340' side='right' caption='[[3f8c]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3f8c]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Laclm Laclm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F8C FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HT1:2-(4-ETHOXYPHENYL)-5-(4-METHYL-1-PIPERAZINYL)-2,5-BI-BENZIMIDAZOLE'>HT1</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3f8b|3f8b]], [[3f8f|3f8f]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lmrR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=416870 LACLM])</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=3f8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f8c OCA], [http://pdbe.org/3f8c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f8c RCSB], [http://www.ebi.ac.uk/pdbsum/3f8c PDBsum]</span></td></tr> | |||
</table> | |||
== 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/f8/3f8c_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=3f8c ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here, we present crystal structures of LmrR in an apo state and in two drug-bound states complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical beta-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a multidrug-binding site. The drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. Multidrug recognition is facilitated by conformational plasticity and the absence of drug-specific hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel shift assays reveal an allosteric coupling between the multidrug- and DNA-binding sites of LmrR that most likely has a function in the induction mechanism. | |||
Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition.,Madoori PK, Agustiandari H, Driessen AJ, Thunnissen AM EMBO J. 2008 Dec 18. PMID:19096365<ref>PMID:19096365</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
< | </div> | ||
<div class="pdbe-citations 3f8c" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Laclm]] | [[Category: Laclm]] | ||
[[Category: Agustiandari, H | [[Category: Agustiandari, H]] | ||
[[Category: Driessen, A J.M | [[Category: Driessen, A J.M]] | ||
[[Category: Madoori, P K | [[Category: Madoori, P K]] | ||
[[Category: Thunnissen, A M.W H | [[Category: Thunnissen, A M.W H]] | ||
[[Category: Transcription regulator]] | [[Category: Transcription regulator]] | ||
[[Category: Winged helix turn helix]] | [[Category: Winged helix turn helix]] | ||
Revision as of 19:24, 9 February 2016
Crystal structure of multidrug binding transcriptional regulator LmrR complexed with Hoechst 33342Crystal structure of multidrug binding transcriptional regulator LmrR complexed with Hoechst 33342
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here, we present crystal structures of LmrR in an apo state and in two drug-bound states complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical beta-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a multidrug-binding site. The drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. Multidrug recognition is facilitated by conformational plasticity and the absence of drug-specific hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel shift assays reveal an allosteric coupling between the multidrug- and DNA-binding sites of LmrR that most likely has a function in the induction mechanism. Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition.,Madoori PK, Agustiandari H, Driessen AJ, Thunnissen AM EMBO J. 2008 Dec 18. PMID:19096365[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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