Deletion of lysine 13 alters the structure and function of parathyroid hormone.
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.
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002872:Chromosome Deletion; D003488:Cyanogen Bromide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D010281:Parathyroid Hormone / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D010446:Peptide Fragments / Q000032:analysis / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine; D008239:Lysine; D003488:Cyanogen Bromide