title: Metal-catalyzed oxidation of protein methionine residues in human parathyroid hormone (1-34): formation of homocysteine and a novel methionine-dependent hydrolysis reaction.
abstract: The oxidation of PTH(1-34) catalyzed by ferrous ethylenediaminetetraacetic acid (EDTA) is site-specific. The oxidation of PTH(1-34) is localized primarily to the residues Met[8] and His[9]. Beyond the transformation of Met[8] and His[9] into methionine sulfoxide and 2-oxo-histidine, respectively, we observed a hydrolytic cleavage between Met[8] and His[9]. This hydrolysis requires the presence of Fe(II) and oxygen and can be prevented by diethylenetriaminepentaacetic acid (DTPA) and phosphate buffer. Conditions leading to this site-specific hydrolysis also promote the transformation of Met[8] into homocysteine, indicating that the hydrolysis and transformation of homocysteine may proceed through a common intermediate.
authors.affiliation: Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas , Lawrence, Kansas 66047, United States.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mozziconacci
authors.forename: Junyan A
authors.initials: JA
authors.lastname: Ji
authors.forename: Y John
authors.initials: YJ
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Schöneich
mesh_terms: D002384:Catalysis; D006710:Homocysteine / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D013058:Mass Spectrometry; D008715:Methionine / Q000737:chemistry*; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000737:chemistry*; D004369:Pentetic Acid / Q000737:chemistry
chemical_list: D010281:Parathyroid Hormone; D006710:Homocysteine; D004369:Pentetic Acid; D008715:Methionine