Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase.

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.

• Authors: Anshika Singhal, Gunjan Arora, Richa Virmani, Parijat Kundu, Tanya Khanna, Andaleeb Sajid, Richa Misra, Jayadev Joshi, Vikas Yadav, Sintu Samanta, Neeru Saini, Amit K Pandey, Sandhya S Visweswariah, Christian Hentschker, Dörte Becher, Ulf Gerth, Yogendra Singh
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 43 Pg. 26218-34 (Oct 23 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26350458 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Phosphoric Monoester Hydrolases

Topics

• Acylation
• Amino Acid Sequence
• Molecular Sequence Data
• Mycobacterium tuberculosis (enzymology, metabolism)
• Phosphoric Monoester Hydrolases (chemistry, metabolism)
• Phosphorylation
• Protein Conformation
• Sequence Homology, Amino Acid
• Structure-Activity Relationship