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 pK 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.

journal_name

Mol Cell Endocrinol

authors

Zull JE,Smith LM,Chuang J,Jentoft J

doi

10.1016/0303-7207(87)90037-2

subject

Has Abstract

pub_date

1987-06-01 00:00:00

pages

267-71

issue

3

eissn

0303-7207

issn

1872-8057

journal_volume

51

pub_type

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