Taken together, these observations highlight the critical role of multiple decorating loops in HisA, PriA and TrpF in facilitating catalysis. These enzymes stand out from prior systems that have been demonstrated to be activated by ligand-gated conformational changes due to a number of factors. First, we have shown the inter-dependent motion of three long loops (or two in TrpF), none of which dominates and each of which is capable of undergoing substantial conformational changes to facilitate the turnover of different substrates. Second, unlike prior systems which show substantial rate accelerations compared to the uncatalyzed reactions with comparatively rapid loop motions, in these enzymes, the catalyzed reaction is already intrinsically fast whereas loop-motion is slow and appears to be controlling the reaction rate.