We note the similarity of these gripper interactions to corresponding interactions in enzymes such as TIM, OMPDC and GPDH, where interactions with the non-reactive phosphodianion group of the substrate drives a ligand-gated conformational change. This in turn stabilizes otherwise energetically unfavorable but catalytically important closed conformations of key catalytic loops over the respective active sites of these enzymes. In the case of the current systems, the interaction between the HisA gripper residues and the remote phosphodianion group of ProFAR appears to be similarly important for maintaining the closed conformation of loop 5, and when this interaction is lost, as in PriA, we see corresponding opening of loop 5 (Figure ). This supports the likelihood that HisA and PriA are also activated by ligand-gated conformational changes, albeit with more complex loop dynamics (due to the involvement of not one but three highly mobile and long catalytic loops) than in other previously characterized systems.