Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase.
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.
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Anshika
A
Singhal
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India, the Translational Health Science and Technology Institute, Faridabad 121001, India.
Gunjan
G
Arora
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Richa
R
Virmani
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Parijat
P
Kundu
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Tanya
T
Khanna
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Andaleeb
A
Sajid
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Richa
R
Misra
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Jayadev
J
Joshi
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Vikas
V
Yadav
the Indian Institute of Science, Bangalore 560012, India, and.
Sintu
S
Samanta
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
Neeru
N
Saini
the Translational Health Science and Technology Institute, Faridabad 121001, India, amitpandey@thsti.res.in.
Amit K
AK
Pandey
the Indian Institute of Science, Bangalore 560012, India, and.
Sandhya S
SS
Visweswariah
the Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, D-17487 Greifswald, Germany.
Christian
C
Hentschker
the Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, D-17487 Greifswald, Germany.
Dörte
D
Becher
the Institute of Microbiology, Ernst-Moritz-Arndt-University Greifswald, D-17487 Greifswald, Germany ulf.gerth@uni-greifswald.de.
Ulf
U
Gerth
From the CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India, ysingh@igib.res.in.
Yogendra
Y
Singh
D000215:Acylation; D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D010744:Phosphoric Monoester Hydrolases
Mycobacterium tuberculosis; bacterial signal transduction; l modifications; mass spectrometry (MS); phosphatase; post-translation modification; propionylation; protein acylation; succinylation