YcgC represents a new protein deacetylase family in prokaryotes
Shun Tu,
Shu-Juan Guo,
Chien-Sheng Chen,
Cheng-Xi Liu,
He-Wei Jiang,
Feng Ge,
Jiao-Yu Deng,
Yi-Ming Zhou,
Daniel M Czajkowsky,
Yang Li,
Bang-Ruo Qi,
Young-Hoon Ahn,
Philip A Cole,
Heng Zhu,
Sheng-Ce Tao
Affiliations
Shun Tu
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
Shu-Juan Guo
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
Chien-Sheng Chen
Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan
Cheng-Xi Liu
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
He-Wei Jiang
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
Feng Ge
Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China
Jiao-Yu Deng
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
Yi-Ming Zhou
National Engineering Research Center for Beijing Biochip Technology, Beijing, China
Daniel M Czajkowsky
Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
Yang Li
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
Bang-Ruo Qi
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
Young-Hoon Ahn
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Philip A Cole
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Heng Zhu
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, United States; The High-Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, United States
Sheng-Ce Tao
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai, China; Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a ‘clip-chip’ strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome. In-depth biochemical characterization confirmed that YcgC is a serine hydrolase involving Ser200 as the catalytic nucleophile for lysine deacetylation and does not use NAD+ or Zn2+ like other established KDACs. Further, in vivo characterization demonstrated that YcgC regulates transcription by catalyzing deacetylation of Lys52 and Lys62 of a transcriptional repressor RutR. Importantly, YcgC targets a distinct set of substrates from the only known E. coli KDAC CobB. Analysis of YcgC’s bacterial homologs confirmed that they also exhibit KDAC activity. YcgC thus represents a novel family of prokaryotic KDACs.
