A comparative molecular field analysis (COMFA) of the structural determinants of heat-stable enterotoxins mediating activation of guanylyl cyclase C.

The heat-stable enterotoxin binds to and activates guanylyl cyclase C (GC-C), regulating fluid and electrolyte secretion in intestinal epithelial cells. A COMFA model was developed to predict the primary interactions between GC-C agonists and their receptor. This model predicts that the amide backbone of Cys 5 -Cys 6 -Glu 7 -Leu 8 , the ‚ carbon atoms of Cys 5 -Cys 6 , and the side chains of Pro 12 , Ala 13 , and Ala 15 comprise the primary interactions of GC-C agonists with the receptor surface.