Mutation of Methionine to Asparagine but Not Leucine in Parathyroid Hormone Mimics the Loss of Biological Function upon Oxidation.

Human parathyroid hormone (PTH) is an 84-amino acid peptide that contains two methionine (Met) residues located at positions 8 and 18. It has long been recognized that Met residues in PTH are subject to oxidation to become Met sulfoxide, resulting in a decreased biological function of the peptide. However, the mechanism of the lost biological function of PTH oxidation remains elusive. To characterize whether the shift from the hydrophobic nature of the native Met residue to the hydrophilic nature of Met sulfoxide plays a role in the reduction of biological activity upon PTH oxidation, we conducted