1. Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase
- Author
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Amit K. Pandey, Anshika Singhal, Richa Virmani, Andaleeb Sajid, Ulf Gerth, Neeru Saini, Christian Hentschker, Yogendra Singh, Parijat Kundu, Sintu Kumar Samanta, Sandhya S. Visweswariah, Vikas Yadav, Tanya Khanna, Doerte Becher, Gunjan Arora, Richa Misra, and Jayadev Joshi
- Subjects
Protein Conformation ,Acylation ,Molecular Sequence Data ,Phosphatase ,Lysine ,Biology ,Microbiology ,complex mixtures ,Biochemistry ,Structure-Activity Relationship ,Protein acylation ,Succinylation ,Protein structure ,Amino Acid Sequence ,Phosphorylation ,Molecular Biology ,Sequence Homology, Amino Acid ,Mycobacterium smegmatis ,Mycobacterium tuberculosis ,Cell Biology ,biology.organism_classification ,Phosphoric Monoester Hydrolases ,Acetylation ,bacteria - Abstract
Protein lysine acetylation is known to regulate multiple aspects of bacterial metabolism. However, its presence in mycobacterial signal transduction and virulence-associated proteins has not been studied. In this study, analysis of mycobacterial proteins from different cellular fractions indicated dynamic and widespread occurrence of lysine acetylation. Mycobacterium tuberculosis proteins regulating diverse physiological processes were then selected and expressed in the surrogate host Mycobacterium smegmatis. The purified proteins were analyzed for the presence of lysine acetylation, leading to the identification of 24 acetylated proteins. In addition, novel lysine succinylation and propionylation events were found to co-occur with acetylation on several proteins. Protein-tyrosine phosphatase B (PtpB), a secretory phosphatase that regulates phosphorylation of host proteins and plays a critical role in Mycobacterium infection, is modified by acetylation and succinylation at Lys-224. This residue is situated in a lid region that covers the enzyme's active site. Consequently, acetylation and succinylation negatively regulate the activity of PtpB.
- Published
- 2015
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