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| | ==Crystal structure of S. aureus MepR-DNA complex== | | ==Crystal structure of S. aureus MepR-DNA complex== |
| - | <StructureSection load='4lln' size='340' side='right' caption='[[4lln]], [[Resolution|resolution]] 2.84Å' scene=''> | + | <StructureSection load='4lln' size='340' side='right'caption='[[4lln]], [[Resolution|resolution]] 2.84Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lln]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lln]] is a 12 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=4LLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LLN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lll|4lll]]</td></tr> | + | </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=4lln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lln OCA], [https://pdbe.org/4lln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lln RCSB], [https://www.ebi.ac.uk/pdbsum/4lln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lln ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mepR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
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| - | <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=4lln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lln OCA], [http://pdbe.org/4lln PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lln RCSB], [http://www.ebi.ac.uk/pdbsum/4lln PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lln ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q5Y812_STAAU Q5Y812_STAAU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Birukou, I]] | + | [[Category: Large Structures]] |
| - | [[Category: Brennan, R G]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Mepr operator]] | + | [[Category: Birukou I]] |
| - | [[Category: Multidrug resistance]] | + | [[Category: Brennan RG]] |
| - | [[Category: Transcription repression]]
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| - | [[Category: Transcription-dna complex]]
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| - | [[Category: Winged helix-turn-helix]]
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| Structural highlights
Function
Q5Y812_STAAU
Publication Abstract from PubMed
The multidrug efflux pump MepA is a major contributor to multidrug resistance in Staphylococcus aureus. MepR, a member of the multiple antibiotic resistance regulator (MarR) family, represses mepA and its own gene. Here, we report the structure of a MepR-mepR operator complex. Structural comparison of DNA-bound MepR with 'induced' apoMepR reveals the large conformational changes needed to allow the DNA-binding winged helix-turn-helix motifs to interact with the consecutive major and minor grooves of the GTTAG signature sequence. Intriguingly, MepR makes no hydrogen bonds to major groove nucleobases. Rather, recognition-helix residues Thr60, Gly61, Pro62 and Thr63 make sequence-specifying van der Waals contacts with the TTAG bases. Removing these contacts dramatically affects MepR-DNA binding activity. The wings insert into the flanking minor grooves, whereby residue Arg87, buttressed by Asp85, interacts with the O2 of T4 and O4' ribosyl oxygens of A23 and T4. Mutating Asp85 and Arg87, both conserved throughout the MarR family, markedly affects MepR repressor activity. The His14':Arg59 and Arg10':His35:Phe108 interaction networks stabilize the DNA-binding conformation of MepR thereby contributing significantly to its high affinity binding. A structure-guided model of the MepR-mepA operator complex suggests that MepR dimers do not interact directly and cooperative binding is likely achieved by DNA-mediated allosteric effects.
Structural mechanism of transcription regulation of the Staphylococcus aureus multidrug efflux operon mepRA by the MarR family repressor MepR.,Birukou I, Seo SM, Schindler BD, Kaatz GW, Brennan RG Nucleic Acids Res. 2014 Feb;42(4):2774-88. doi: 10.1093/nar/gkt1215. Epub 2013, Nov 28. PMID:24293644[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Birukou I, Seo SM, Schindler BD, Kaatz GW, Brennan RG. Structural mechanism of transcription regulation of the Staphylococcus aureus multidrug efflux operon mepRA by the MarR family repressor MepR. Nucleic Acids Res. 2014 Feb;42(4):2774-88. doi: 10.1093/nar/gkt1215. Epub 2013, Nov 28. PMID:24293644 doi:http://dx.doi.org/10.1093/nar/gkt1215
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