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bioRxiv · 10.1101/2024.03.22.586220

Aeromonas hydrophila CobQ is a new type of NAD+- and Zn2+-independent protein lysine deacetylase in prokaryotes

Wang, Y.·Wang, G.·Zhang, L.·Cai, Q.·Lin, M.·Huang, D.·Xie, Y.·Lin, W.·Lin, X.
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Abstract

Protein N--lysine acetylation (Kac) modifications play crucial roles in diverse physiological and pathological functions in cells. In prokaryotic cells, there are only two types of lysine deacetylases (KDACs) that are Zn2+- or NAD+-dependent. In this study, we reported a protein, AhCobQ, in Aeromonas hydrophila ATCC 7966 that presents NAD+- and Zn2+-independent KDAC activity. Furthermore, its KDAC activity is located in an unidentified domain (from 195-245 aa). Interestingly, AhCobQ has no homology with current known KDACs, and no homologous protein was found in eukaryotic cells. A protein substrate analysis showed that AhCobQ has specific protein substrates in common with other known KDACs, indicating that these KDACs can dynamically co-regulate the states of Kac proteins. Microbiological methods employed in this study affirmed AhCobQs positive regulation of isocitrate dehydrogenase (ICD) enzymatic activity at the K388 site, implicating AhCobQ in the modulation of bacterial enzymatic activities. In summary, our findings present compelling evidence that AhCobQ represents a distinctive type of KDAC with significant roles in bacterial biological functions. SummaryThe lack of exploration of new lysine acetylases and deacetylases (KDACs) and their protein substrates in prokaryotic cells has become a bottleneck in the functional study of lysine acetylation modifications. In this study, we reported a novel Zn2+- and NAD+-independent KDAC protein, AhCobQ, in Aeromonas hydrophila. Interestingly, this protein does not share homology with current known KDACs, and its KDAC activity is located in an unknown domain for which a homologous protein cannot be found in eukaryotic cells. The following analysis showed that AhCobQ affected the enzymatic activity and protein-protein interaction ability of its protein substrates. In summary, these results extended our understanding of the regulatory mechanism of bacterial lysine acetylation modifications. HighlightsAhCobQ is an NAD+- and Zn2+-independent protein lysine deacetylase. There are no proteins homologous to AhCobQ in eukaryotes. The deacetylase activity of AhCobQ is located in an unknown domain. AhCobQ has specific protein substrates and substrates in common with other lysine deacetylases. AhCobQ positively regulates the enzymatic activity of isocitrate dehydrogenase at its K388 site.

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Wang, Y., Wang, G., Zhang, L., Cai, Q., Lin, M., Huang, D., Xie, Y., Lin, W., Lin, X.. 2024-03-22. Aeromonas hydrophila CobQ is a new type of NAD+- and Zn2+-independent protein lysine deacetylase in prokaryotes. https://doi.org/10.1101/2024.03.22.586220

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