| Literature DB >> 24703693 |
Minjia Tan1, Chao Peng2, Kristin A Anderson3, Peter Chhoy3, Zhongyu Xie2, Lunzhi Dai2, Jeongsoon Park4, Yue Chen2, He Huang2, Yi Zhang1, Jennifer Ro5, Gregory R Wagner3, Michelle F Green3, Andreas S Madsen6, Jessica Schmiesing7, Brett S Peterson3, Guofeng Xu2, Olga R Ilkayeva3, Michael J Muehlbauer3, Thomas Braulke7, Chris Mühlhausen7, Donald S Backos8, Christian A Olsen6, Peter J McGuire9, Scott D Pletcher5, David B Lombard4, Matthew D Hirschey10, Yingming Zhao11.
Abstract
We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.Entities:
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Year: 2014 PMID： 24703693 PMCID： PMC4108075 DOI： 10.1016/j.cmet.2014.03.014
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287