View source for 4zzl


==MexR R21W derepressor mutant causing multidrug resistance in P. aeruginosa by mexAB-oprM efflux pump expression==
<StructureSection load='4zzl' size='340' side='right'caption='[[4zzl]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zzl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZZL 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]] 2.19&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4zzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zzl OCA], [https://pdbe.org/4zzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zzl RCSB], [https://www.ebi.ac.uk/pdbsum/4zzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zzl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MEXR_PSEAE MEXR_PSEAE] Repressor of the mexAB-oprM multidrug resistance operon. Also represses its own expression. Many variants lead to increased expression of the mexAB-oprM operon.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 A) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members.

Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.,Anandapadamanaban M, Pilstal R, Andresen C, Trewhella J, Moche M, Wallner B, Sunnerhagen M Structure. 2016 Jul 13. pii: S0969-2126(16)30133-2. doi:, 10.1016/j.str.2016.06.008. PMID:27427478<ref>PMID:27427478</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zzl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Anandapadamanaban M]]
[[Category: Moche M]]
[[Category: Pilstal R]]
[[Category: Sunnerhagen M]]
[[Category: Wallner B]]
[[Category: Ziauddin JME]]