Metal-Catalyzed Oxidation of Protein Methionine Residues in Human Parathyroid Hormone (1-34): Formation of Homocysteine and a Novel Methionine-Dependent Hydrolysis Reaction

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• 作者：Olivier Mozziconacci ; Junyan A. Ji ; Y. John Wang ; Christian Sch枚neich
• 刊名：Molecular Pharmaceutics
• 出版年：2013
• 出版时间：February 4, 2013
• 年：2013
• 卷：10
• 期：2
• 页码：739-755
• 全文大小：870K
• 年卷期：v.10,no.2(February 4, 2013)
• ISSN：1543-8392

文摘

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.

Keywords:

parathyroid hormone; alanine; methionine; homocysteine; methionine radical cation; Fenton reaction; hydrolysis; mass spectrometry