View source for 5hev


==Crystal Structure of the beryllofluoride-activated LiaR from Enterococcus faecium==
<StructureSection load='5hev' size='340' side='right' caption='[[5hev]], [[Resolution|resolution]] 3.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hev]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HEV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4if4|4if4]]</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=5hev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hev OCA], [http://pdbe.org/5hev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hev RCSB], [http://www.ebi.ac.uk/pdbsum/5hev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hev ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cyclic antimicrobial lipopeptide daptomycin (DAP) triggers the LiaFSR membrane stress response pathway in enterococci and many other Gram-positive organisms. LiaR is the response regulator that, upon phosphorylation, binds in a sequence-specific manner to DNA to regulate transcription in response to membrane stress. In clinical settings, non-susceptibility to DAP by Enterococcus faecium is correlated frequently with a mutation in LiaR of Trp73 to Cys (LiaRW73C). We have determined the structure of the activated E. faecium LiaR protein at 3.2A resolution and, in combination with solution studies, show that the activation of LiaR induces the formation of a LiaR dimer that increases LiaR affinity at least 40-fold for the extended regulatory regions upstream of the liaFSR and liaXYZ operons. In vitro, LiaRW73C induces phosphorylation-independent dimerization of LiaR and provides a biochemical basis for non-susceptibility to DAP by the upregulation of the LiaFSR regulon. A comparison of the E. faecalis LiaR, E. faecium LiaR, and the LiaR homolog from Staphylococcus aureus (VraR) and the mutations associated with DAP resistance suggests that physicochemical properties such as oligomerization state and DNA specificity, although tuned to the biology of each organism, share some features that could be targeted for new antimicrobials.

An Adaptive Mutation in Enterococcus faecium LiaR Associated with Antimicrobial Peptide Resistance Mimics Phosphorylation and Stabilizes LiaR in an Activated State.,Davlieva M, Tovar-Yanez A, DeBruler K, Leonard PG, Zianni MR, Arias CA, Shamoo Y J Mol Biol. 2016 Nov 6;428(22):4503-4519. doi: 10.1016/j.jmb.2016.09.016. Epub, 2016 Sep 23. PMID:27670715<ref>PMID:27670715</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5hev" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Davlieva, M]]
[[Category: Shamoo, Y]]
[[Category: Enterococcus faecium]]
[[Category: Liar]]
[[Category: Response regulator]]
[[Category: Transcription]]