Working model for VanR_A-VanS_A signaling.

A schematic view is shown for the VanS_A protein. The protein comprises three domains: The sensor domain (gray), which includes two predicted transmembrane helices and is responsible for sensing the inducing signal; the dimerization & histidine-phosphotransfer (DHp) domain (green), which includes the conserved histidine that is the site of autophosphorylation; and the catalytic (CA) domain (magenta), which binds nucleotide triphosphate and is responsible for catalyzing histidine phosphorylation. In the absence of vancomycin, VanS_A acts as a phosphatase, keeping VanR_A in an inactive, dephosphorylated state. Vancomycin induces VanS_A to autophosphorylate, after which phospho-VanS_A transfers the phosphoryl group to VanR_A. Finally, phospho-VanR_A activates transcription of the van resistance genes.