While both wild-type PriA and HisA are capable of catalyzing isomerization of the substrate ProFAR, only PriA can catalyze the isomerization of the smaller substrate PRA. As already seen from the PriA crystal structures with both products bound, loop 5 can be rearranged either to accommodate one substrate or the other, displaying two slightly different conformations of the loop (Figure ). These are a "knot-like" pro-ProFAR conformation of loop 5, with W145