4if4
Crystal Structure of the Magnesium and beryllofluoride-activated VraR from Staphylococcus aureusCrystal Structure of the Magnesium and beryllofluoride-activated VraR from Staphylococcus aureus
Structural highlights
Function[VRAR_STAAM] Member of the two-component regulatory system VraS/VraR involved in the control of the cell wall peptidoglycan biosynthesis. VraR is overexpressed in strain Mu50, which leads to vancomycin resistance. Publication Abstract from PubMedStaphylococcus aureus VraR, a vancomycin-resistance-associated response regulator, activates a cell-wall-stress stimulon in response to antibiotics that inhibit cell wall formation. X-ray crystal structures of VraR in both unphosphorylated and beryllofluoride-activated states have been determined, revealing a mechanism of phosphorylation-induced dimerization that features a deep hydrophobic pocket at the center of the receiver domain interface. Unphosphorylated VraR exists in a closed conformation that inhibits dimer formation. Phosphorylation at the active site promotes conformational changes that are propagated throughout the receiver domain, promoting the opening of a hydrophobic pocket that is essential for homodimer formation and enhanced DNA-binding activity. This prominent feature in the VraR dimer can potentially be exploited for the development of novel therapeutics to counteract antibiotic resistance in this important pathogen. Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation.,Leonard PG, Golemi-Kotra D, Stock AM Proc Natl Acad Sci U S A. 2013 May 21;110(21):8525-30. doi:, 10.1073/pnas.1302819110. Epub 2013 May 6. PMID:23650349[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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