Deletion of lysine 13 alters the structure and function of parathyroid hormone

Abstract

A peptide of unknown structure was found as a side product in a commercial preparation of the 1–34 fragment of bovine parathyroid hormone (PTH). CNBr cleavage and amino acid analysis showed that this peptide is the des-lys-13 form of 1–34 bovine PTH. The peptide thus represents a deletion mutant of PTH and structure-function studies are of interest. This peptide was a full agonist in the adenylyl cyclase bioassay for PTH, but its potency was about 5% of that found for the complete 1–34 peptide. Proton NMR studies showed that the p K values for the histidine residues in the des-lys-13 form were essentially identical to those of the intact peptide. However, pH-dependent changes in the chemical shifts for the tryptophan protons (residue 23) and several unidentified methyl group resonances were observed in the des-lys peptide. The latter are major shifts and probably represent ring-current effects; these were not seen in the intact 1–34 peptide. The results show that Lys-13 is important in the folding of the active domain of PTH, and are interpreted in the context of a previously published model for the folding of this hormone.