8DVQ

CA domain of VanSA histidine kinase

Summary for 8DVQ

• Entry DOI: 10.2210/pdb8dvq/pdb
• Descriptor: Sensor protein VanS, CADMIUM ION (3 entities in total)
• Functional Keywords: atp-binding, histidine kinase, signaling protein
• Biological source: Enterococcus
• Total number of polymer chains: 1
• Total formula weight: 18480.33

Authors

Loll, P.J. (deposition date: 2022-07-29, release date: 2023-03-22, Last modification date: 2024-05-22)

Primary citation

Grasty, K.C.,Guzik, C.,D'Lauro, E.J.,Padrick, S.B.,Beld, J.,Loll, P.J.
Structure of VanS from vancomycin-resistant enterococci: A sensor kinase with weak ATP binding.
J.Biol.Chem., 299:103001-103001, 2023

PubMed Abstract: The VanRS two-component system regulates the resistance phenotype of vancomycin-resistant enterococci. 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 vancomycin-resistant enterococci 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.

PubMed: 36764524
DOI: 10.1016/j.jbc.2023.103001

Experimental method

X-RAY DIFFRACTION (2.19 Å)