Figure 3.

GUCY2C Ligands. The four members of the guanylin protein family are guanylin and uroguanylin, found in humans, and renoguanylin and lymphoguanylin, found in other species. While the first three have a structural conformation characterized by two disulfide bonds (yellow), lymphoguanylin lacks the C-terminal cysteine (green), and therefore has only one disulfide bond. A mutant guanylin (C115Y) similarly has only one disulfide bond and lower potency of GUCY2C activation. In contrast, bacterial ST is characterized by a rigid structure with three disulfide bonds. Synthetic GUCY2C agonists include plecanatide and dolcanatide (uroguanylin analogs), and linaclotide (ST analog). Amino acid differences between these analogs and the parent compound are shown in red.