The bond with His-254 does not occur with natural peptide substrate and may have the unwanted effect of altering the conformation of the histidine or the inhibitor. the side chains of Tyr-205 and Trp-236 within the substrate-binding groove. The formation of the tetrahedral adduct is also accompanied by LY2794193 opening … Continue reading The bond with His-254 does not occur with natural peptide substrate and may have the unwanted effect of altering the conformation of the histidine or the inhibitor