Abstract:

E. coli heat stable enterotoxin STa is an agonist of the membrane guanylate cyclase C whose endogenous ligands are the peptide hormones guanylin and uroguanylin. Whereas these peptides contain only two disulfide bonds, STa is stabilized by one additional disulfide bridge. We chemically synthesized the enterotoxin STh that originates from the E. coli strain found in humans, and we determined its structure and its dynamics by nuclear magnetic resonance spectroscopy and molecular dynamics calculations. Chemical synthesis clearly proved successful and resulted in the formation of the native disulfide bonds. The endogenous ligands guanylin and uroguanylin show the same general structural features and dynamics properties as the enterotoxin.