5hev | pdb_00005hev

Crystal Structure of the beryllofluoride-activated LiaR from Enterococcus faecium

spinqualitylabelsall models 5hev, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hev is a 4 chain structure with sequence from Enterococcus faecium SD3B-2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.192Å Ligands: BEF, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S4FAU8_ENTFC 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Response regulator 3D structure

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