Journal article
Structure of VanS from Vancomycin-Resistant Enterococci: A Sensor Kinase with Weak ATP Binding
The Journal of biological chemistry, v 299(3), 103001
08 Feb 2023
PMID: 36764524
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The VanRS two-component system regulates the resistance phenotype of vancomycin-resistant enterococci (VRE). VanS is a sensor histidine kinase that responds to the presence of vancomycin by autophosphorylating and subsequently transferring the phosphoryl group to the response regulator, VanR. The phosphotransfer activates VanR as a transcription factor, which initiates the expression of resistance genes. Structural information about VanS proteins has remained elusive, hindering the molecular-level understanding of their function. Here, we present X-ray crystal structures for the catalytic and ATP-binding (CA) domains of two VanS proteins, derived from VRE types A and C. Both proteins adopt the canonical Bergerat fold that has been observed for CA domains of other prokaryotic histidine kinases. We attempted to determine structures for the nucleotide-bound forms of both proteins; however, despite repeated efforts, these forms could not be crystallized, prompting us to measure the proteins' binding affinities for ATP. Unexpectedly, both CA domains displayed low affinities for the nucleotide, with K
values in the low millimolar range. Since these K
values are comparable to intracellular ATP concentrations, this weak substrate binding could reflect a way of regulating expression of the resistance phenotype.
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Details
- Title
- Structure of VanS from Vancomycin-Resistant Enterococci: A Sensor Kinase with Weak ATP Binding
- Creators
- Kimberly C Grasty - Drexel UniversityClaudia Guzik - Drexel UniversityElizabeth J D'Lauro - Drexel UniversityShae B Padrick - Drexel UniversityJoris Beld - Drexel UniversityPatrick J Loll - Drexel University
- Publication Details
- The Journal of biological chemistry, v 299(3), 103001
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Microbiology and Immunology
- Web of Science ID
- WOS:001009293500001
- Scopus ID
- 2-s2.0-85149755585
- Other Identifier
- 991020060583504721
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- Web of Science research areas
- Biochemistry & Molecular Biology