4GVP

Crystal Structure of the Response Regulator Protein VraR from Staphylococcus aureus

Summary for 4GVP

• Entry DOI: 10.2210/pdb4gvp/pdb
• Descriptor: Response regulator protein vraR (2 entities in total)
• Functional Keywords: response regulator, two-component system, bacterial signalling, dna binding, transcription factor, transcription
• Biological source: Staphylococcus aureus
• Cellular location: Cytoplasm (Potential): Q7A2Q1
• Total number of polymer chains: 4
• Total formula weight: 93840.58

Authors

Leonard, P.G.,Stock, A.M. (deposition date: 2012-08-31, release date: 2013-05-08, Last modification date: 2024-02-28)

Primary citation

Leonard, P.G.,Golemi-Kotra, D.,Stock, A.M.
Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation.
Proc.Natl.Acad.Sci.USA, 110:8525-8530, 2013

PubMed Abstract: 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.

PubMed: 23650349
DOI: 10.1073/pnas.1302819110

Experimental method

X-RAY DIFFRACTION (2.03 Å)