"The inhibitors that we discuss here and in the main text all have a pair of rings on each side of the central sulfonamide group; the exception is JEDI-852, which lacks ring 1. The conformation of the sulfonamide group results in a rapid change in direction at this point. The side chains that interact with rings 1, 2 and the inward-directed face of ring 3 of the inhibitor are essentially unchanged in conformation when compared to the EcLpxH/product complex, whether in complex with EcLpxH or KpLpxH. The largest outlier is the piperazine ring of JEDI-852, which because it lacks the aromatic ring 1, is able to make a small re-orientation in ring 2, which presumably optimizes the interaction with the enzyme" [See Supplementary for Full Response] 3 Results