Two mechanisms have been proposed to explain how carbohydrate inhibits receptor-binding activity of glycoprotein hormones: 1) blocking of access to the receptor by steric hindrance on the part of the oligosaccharide or 2) alteration in hormone conformation following deglycosy-lation that increases receptor-binding affinity. The latter mechanism is based in part on low-resolution circular di-chroism studies. Carbohydrate-induced changes in conformation appear less likely on the basis of the results of recent x-ray crystallographic and NMR studies on hCG. birth control pills
The conformational change in hCGa subunit following dissociation from hCG reportedly involved loss of all secondary structure, two p strands, and a short a helix in the long loop L2. In the same study, enzymatic deglycosylation, which removed all but the proximal GlcNAc residue from both glycosylation sites, caused no notable difference in the protein conformation of the deglycosylated a-subunit derivative from that of intact hCGa. The crystal structure of chemically deglycosylated hCG suggested hydrogen bonding between the residual Asn52 oligosaccharide and some hCGp residues.