Fig. 3. Comparison of the crystal structure of 1 (pink) bound to PvNMT (yellow) and 13 (blue) bound to LmNMT (grey). (A) Overlay of 1 in PvNMT and 13 in LdNMT, with the enzymes removed for clarity; the phenyl ring of the benzo[b]thiophene scaffold protrudes in the direction of potential 3- and 4-substitutions of the phenyl series. (B) The surface of the active site of LmNMT (grey) shows a constrained, water filled back pocket in the same position as that occupied by the benzo[b]thiophene. (C) Alanine to methionine substitution in LmNMT results in a more constrained pocket and a potential clash with the bulkier benzothiophene scaffold.