Dehomocysteinylation is catalysed by the sirtuin‐2‐like bacterial lysine deacetylase CobB

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• 作者：Xin‐Yu Mei ; Xia‐Di He ; Lei Huang ; Da‐Shi Qi ; Ji Nie ; Yang Li ; Wen Si ; Shi‐Min Zhao
• 刊名：FEBS Journal
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：283
• 期：22
• 页码：4149-4162
• 全文大小：765.2KB
• ISSN：1742-4658

文摘

Hyperhomocysteinemia, which is characterized by elevated blood levels of the non-protein amino acid homocysteine (Hcy), is an independent risk factor for many diseases, including cardiovascular diseases, neurodegenerative diseases and birth defects. The incorporation of homocysteine into proteins, known as protein N-homocysteinylation, has been considered a major mechanism that contributes to hyperhomocysteinemia. However, the process of dehomocysteinylation, the N-homocysteinylation substrates and the regulatory enzyme(s) remain largely unknown. In this study, we observed that the dehomocysteinylation reaction is a spontaneous process that can be inhibited by blocking –SH groups, which have been demonstrated to be critical for non-enzymatic dehomocysteinylation reactions. We also report that CobB, a known Sir2-like bacterial lysine deacetylase, catalyzes lysine dehomocysteinylation reactions both in vitro and in vivo. Our work provides insight into how this non-enzymatic modification might be removed from affected proteins, supplies potential targets for developing identification methods for N-homocysteine proteins, and identifies CobB as the first prokaryotic dehomocysteinylation enzyme.