MODELING THE PEPTIDE RECEPTOR INTERACTION - SELECTIVITY OF THE OXYTOCIN RECEPTOR

In this study the interactions of oxytocin with the transmembrane regi on of the oxytocin receptor were modelled in order to explain the sele ctive binding of oxytocin and vasopressin. Three sites of interaction in the receptors were identified by sequence comparison and model buil ding. Both receptors share one site, which is formed by glutamine resi dues. This site binds the Asn-5 common to both hormones. The second si te is a specific hydrophobic pocket formed by isoleucine and phenylala nine residues. A third interaction is between a conserved tyrosine and the glutamine of vasopressin and oxytocin. The model suggests that on e receptor residue in the transmembrane region is responsible for the specificity of the receptors. The model may be used in the rational de sign of non peptide analogues for the hormones. (C) 1994 Academic Pres s, Inc.