Figure 7.

Proposed model for response regulator DNA binding and 2-AI binding. In solution, response regulators are predominantly in the “tucked” conformation. In the absence of inhibitor, the response regulator is free to move the C-terminal domains. This assists in binding the target DNA and allows the N-terminal domain to “kneel” over one of the DNA-binding domains. Binding of a 2-AI compound likely increases the interactions between the N- and C-terminal domains, impacting the protein's ability to position both DNA-binding domains on the promotor substrate and “kneel” over the N-terminal domain. Interfering with DNA binding or the protein conformation on the DNA would be expected to reduce the expression of downstream targets.