Structural highlights
Publication Abstract from PubMed
Staphylococcus 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 Also
References
- ↑ Leonard PG, Golemi-Kotra D, Stock AM. Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation. 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 doi:10.1073/pnas.1302819110
