Differential Binding of Desmopressin and Vasopressin to Neurophysin-II
Year: 1996
Type: article
Abstract: Desmopressin is a synthetic analog of the peptide hormone vasopressin in which the N-terminal alpha-amino group has been removed and L-arginine in position 8 has been replaced by D-arginine. Using 1H-NMR spectroscopy, we show that desmopressin binds to neurophysin-II, whereas deamino-vasopressin does not bind. Thus, the change in configuration at Arg8 causes a significant difference in the binding of these hormones to neurophysin-II. We have determined the structure of desmopressin bound to neurophysin-II using two-dimensional 1H nuclear magnetic resonance-transferred nuclear Overhauser effect techniques. A common binding motif for vasopressin and desmopressin is proposed that includes a positive charge group along with the hydrophobic surface formed by the side chains of Tyr2 and a beta-methylene provided by Phe-3. In vasopressin, the positive charge is provided by the N-terminal NH3+, whereas in desmopressin, the side chain of Arg-8 contributes the positive charge. The type II beta-turn found in residues Cys6-Pro7-D-Arg8-Gly9 of the bound structure of desmopressin folds the Arg8 side chain back toward the disulfide-bond loop, which allows the positive charged side chain of Arg8 to participate in binding. Such a type II beta-turn is not found in deamino-vasopressin in the presence of neurophysin-II.
Source: Journal of Biological Chemistry
Authors: Jianjun Wang, Esther Breslow, Brian D. Sykes
Institutions: University of Alberta, Cornell University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2050811727