1rkw: Difference between revisions
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< | ==CRYSTAL STRUCTURE OF THE MULTIDRUG BINDING TRANSCRIPTIONAL REPRESSOR QACR BOUND TO PENTAMADINE== | ||
<StructureSection load='1rkw' size='340' side='right'caption='[[1rkw]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1rkw]] 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=1RKW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RKW FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62Å</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNT:1,5-BIS(4-AMIDINOPHENOXY)PENTANE'>PNT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1rkw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rkw OCA], [https://pdbe.org/1rkw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rkw RCSB], [https://www.ebi.ac.uk/pdbsum/1rkw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rkw 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/rk/1rkw_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=1rkw ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The Staphylococcus aureus multidrug-binding protein QacR represses transcription of the plasmid-encoded membrane protein QacA, a multidrug efflux transporter. QacR is induced by multiple structurally dissimilar monovalent and bivalent cationic lipophilic compounds, many of which are effluxed from the cell by QacA via the proton motive force. The multidrug-binding pocket of QacR has been shown to be quite extensive and features several glutamates and multiple aromatic residues. To date, the structure of only one QacR-bivalent cationic drug complex (that of QacR bound to dequalinium) has been determined, and how other longer or shorter bivalent cationic compounds bind is unknown. Here we report the crystal structures of QacR bound to two cytotoxic bivalent diamidines, pentamidine and hexamidine. These compounds are structurally similar, differing by only one methylene carbon in the alkyl chain linker. However, this small difference results in very dissimilar binding modes. Similar to dequalinium, hexamidine spans the multidrug-binding pocket, and its positively charged benzamidine groups are neutralized by residues Glu-57 and Glu-120. Pentamidine binds QacR in a novel fashion whereby one of its benzamidine groups interacts with residue Glu-63, and the other is neutralized by carbonyl and side chain oxygen atoms. Thus, these structures demonstrate that a formal negative charge is not a prerequisite for binding positively charged drugs and underscore the versatility of the QacR and, likely, all multidrug-binding pockets. | |||
Crystal structures of QacR-diamidine complexes reveal additional multidrug-binding modes and a novel mechanism of drug charge neutralization.,Murray DS, Schumacher MA, Brennan RG J Biol Chem. 2004 Apr 2;279(14):14365-71. Epub 2004 Jan 15. PMID:14726520<ref>PMID:14726520</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1rkw" 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: Staphylococcus aureus]] | ||
[[Category: Brennan | [[Category: Brennan RG]] | ||
[[Category: Murray | [[Category: Murray DS]] | ||
[[Category: Schumacher | [[Category: Schumacher MA]] | ||
Latest revision as of 09:05, 23 August 2023
CRYSTAL STRUCTURE OF THE MULTIDRUG BINDING TRANSCRIPTIONAL REPRESSOR QACR BOUND TO PENTAMADINECRYSTAL STRUCTURE OF THE MULTIDRUG BINDING TRANSCRIPTIONAL REPRESSOR QACR BOUND TO PENTAMADINE
Structural highlights
FunctionQACR_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 Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Staphylococcus aureus multidrug-binding protein QacR represses transcription of the plasmid-encoded membrane protein QacA, a multidrug efflux transporter. QacR is induced by multiple structurally dissimilar monovalent and bivalent cationic lipophilic compounds, many of which are effluxed from the cell by QacA via the proton motive force. The multidrug-binding pocket of QacR has been shown to be quite extensive and features several glutamates and multiple aromatic residues. To date, the structure of only one QacR-bivalent cationic drug complex (that of QacR bound to dequalinium) has been determined, and how other longer or shorter bivalent cationic compounds bind is unknown. Here we report the crystal structures of QacR bound to two cytotoxic bivalent diamidines, pentamidine and hexamidine. These compounds are structurally similar, differing by only one methylene carbon in the alkyl chain linker. However, this small difference results in very dissimilar binding modes. Similar to dequalinium, hexamidine spans the multidrug-binding pocket, and its positively charged benzamidine groups are neutralized by residues Glu-57 and Glu-120. Pentamidine binds QacR in a novel fashion whereby one of its benzamidine groups interacts with residue Glu-63, and the other is neutralized by carbonyl and side chain oxygen atoms. Thus, these structures demonstrate that a formal negative charge is not a prerequisite for binding positively charged drugs and underscore the versatility of the QacR and, likely, all multidrug-binding pockets. Crystal structures of QacR-diamidine complexes reveal additional multidrug-binding modes and a novel mechanism of drug charge neutralization.,Murray DS, Schumacher MA, Brennan RG J Biol Chem. 2004 Apr 2;279(14):14365-71. Epub 2004 Jan 15. PMID:14726520[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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