2015
Tu, Shun; Guo, Shu-Juan; Chen, Chien-Sheng; Liu, Cheng-Xi; Jiang, He-Wei; Ge, Feng; Deng, Jiao-Yu; Zhou, Yi-Ming; Czajkowsky, Daniel M; Li, Yang; Qi, Bang-Ruo; Ahn, Young-Hoon; Cole, Philip A; Zhu, Heng; Tao, Sheng-Ce
YcgC represents a new protein deacetylase family in prokaryotes Journal Article
In: Elife, vol. 4, 2015, ISSN: 2050-084X.
Abstract | Links | BibTeX | Tags: Amidohydrolases, Escherichia coli, Escherichia coli Proteins, Lysine, Post-Translational, Protein Processing, Substrate Specificity, Transcription Factors
@article{1299968,
title = {YcgC represents a new protein deacetylase family in prokaryotes},
author = {Shun Tu and Shu-Juan Guo and Chien-Sheng Chen and Cheng-Xi Liu and He-Wei Jiang and Feng Ge and Jiao-Yu Deng and Yi-Ming Zhou and Daniel M Czajkowsky and Yang Li and Bang-Ruo Qi and Young-Hoon Ahn and Philip A Cole and Heng Zhu and Sheng-Ce Tao},
doi = {10.7554/eLife.05322},
issn = {2050-084X},
year = {2015},
date = {2015-12-01},
journal = {Elife},
volume = {4},
abstract = {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 Zn(2+) 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.},
keywords = {Amidohydrolases, Escherichia coli, Escherichia coli Proteins, Lysine, Post-Translational, Protein Processing, Substrate Specificity, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
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 Zn(2+) 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.
Dancy, Beverley M; Cole, Philip A
Protein lysine acetylation by p300/CBP Journal Article
In: Chem Rev, vol. 115, no. 6, pp. 2419-52, 2015, ISSN: 1520-6890.
Links | BibTeX | Tags: Acetylation, Animals, Humans, Lysine, Models, Molecular, p300-CBP Transcription Factors
@article{1299973,
title = {Protein lysine acetylation by p300/CBP},
author = {Beverley M Dancy and Philip A Cole},
doi = {10.1021/cr500452k},
issn = {1520-6890},
year = {2015},
date = {2015-03-01},
journal = {Chem Rev},
volume = {115},
number = {6},
pages = {2419-52},
keywords = {Acetylation, Animals, Humans, Lysine, Models, Molecular, p300-CBP Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
2014
Wang, Yun; Kavran, Jennifer M; Chen, Zan; Karukurichi, Kannan R; Leahy, Daniel J; Cole, Philip A
Regulation of S-adenosylhomocysteine hydrolase by lysine acetylation Journal Article
In: J Biol Chem, vol. 289, no. 45, pp. 31361-72, 2014, ISSN: 1083-351X.
Abstract | Links | BibTeX | Tags: Acetylation, Adenosylhomocysteinase, Amino Acid, Amino Acid Sequence, Catalysis, Crystallography, Humans, Hydrogen Bonding, Lysine, Methylation, Models, Molecular, Molecular Sequence Data, Mutagenesis, NAD, Plasmids, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Recombinant Proteins, Sequence Homology, Site-Directed, Structure-Activity Relationship, Tertiary, X-Ray
@article{1299977,
title = {Regulation of S-adenosylhomocysteine hydrolase by lysine acetylation},
author = {Yun Wang and Jennifer M Kavran and Zan Chen and Kannan R Karukurichi and Daniel J Leahy and Philip A Cole},
doi = {10.1074/jbc.M114.597153},
issn = {1083-351X},
year = {2014},
date = {2014-11-01},
journal = {J Biol Chem},
volume = {289},
number = {45},
pages = {31361-72},
abstract = {S-Adenosylhomocysteine hydrolase (SAHH) is an NAD(+)-dependent tetrameric enzyme that catalyzes the breakdown of S-adenosylhomocysteine to adenosine and homocysteine and is important in cell growth and the regulation of gene expression. Loss of SAHH function can result in global inhibition of cellular methyltransferase enzymes because of high levels of S-adenosylhomocysteine. Prior proteomics studies have identified two SAHH acetylation sites at Lys(401) and Lys(408) but the impact of these post-translational modifications has not yet been determined. Here we use expressed protein ligation to produce semisynthetic SAHH acetylated at Lys(401) and Lys(408) and show that modification of either position negatively impacts the catalytic activity of SAHH. X-ray crystal structures of 408-acetylated SAHH and dually acetylated SAHH have been determined and reveal perturbations in the C-terminal hydrogen bonding patterns, a region of the protein important for NAD(+) binding. These crystal structures along with mutagenesis data suggest that such hydrogen bond perturbations are responsible for SAHH catalytic inhibition by acetylation. These results suggest how increased acetylation of SAHH may globally influence cellular methylation patterns.},
keywords = {Acetylation, Adenosylhomocysteinase, Amino Acid, Amino Acid Sequence, Catalysis, Crystallography, Humans, Hydrogen Bonding, Lysine, Methylation, Models, Molecular, Molecular Sequence Data, Mutagenesis, NAD, Plasmids, Post-Translational, Protein Binding, Protein Processing, Protein Structure, Recombinant Proteins, Sequence Homology, Site-Directed, Structure-Activity Relationship, Tertiary, X-Ray},
pubstate = {published},
tppubtype = {article}
}
S-Adenosylhomocysteine hydrolase (SAHH) is an NAD(+)-dependent tetrameric enzyme that catalyzes the breakdown of S-adenosylhomocysteine to adenosine and homocysteine and is important in cell growth and the regulation of gene expression. Loss of SAHH function can result in global inhibition of cellular methyltransferase enzymes because of high levels of S-adenosylhomocysteine. Prior proteomics studies have identified two SAHH acetylation sites at Lys(401) and Lys(408) but the impact of these post-translational modifications has not yet been determined. Here we use expressed protein ligation to produce semisynthetic SAHH acetylated at Lys(401) and Lys(408) and show that modification of either position negatively impacts the catalytic activity of SAHH. X-ray crystal structures of 408-acetylated SAHH and dually acetylated SAHH have been determined and reveal perturbations in the C-terminal hydrogen bonding patterns, a region of the protein important for NAD(+) binding. These crystal structures along with mutagenesis data suggest that such hydrogen bond perturbations are responsible for SAHH catalytic inhibition by acetylation. These results suggest how increased acetylation of SAHH may globally influence cellular methylation patterns.