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 beta 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.
Wolfe
Henry R
HR
Targeted Diagnostics and Therapeutics, Inc., 1045 Andrew Drive, West Chester, Pennsylvania 19380, USA. Wolfe@tdtinc.com
Waldman
Scott A
SA
D000595:Amino Acid Sequence; D004768:Enterotoxins / Q000737:chemistry*; D006162:Guanylate Cyclase / Q000737:chemistry*; D006358:Hot Temperature; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000819:agonists* / Q000737:chemistry*
D004768:Enterotoxins; D018000:Receptors, Peptide; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled