Characterization of Phosphopantetheinyl Hydrolase from Mycobacterium tuberculosis
| Autor: | Su Tang, Kristin Burns-Huang, Carl Nathan, Xiuju Jiang, Guangli Yang, Ouathek Ouerfelli, Ben Gold, Annie Geiger, Felipe B. d’Andrea, James C. Sacchettini, Ronnie Bourland, Kyu Y. Rhee, Travis Hartman, Shilpika Pandey, Julia Roberts, Amrita Singh, John W. Mosior |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Tuberculosis Physiology Coenzyme A Virulence Microbiology metallophosphodiesterase Mycobacterium tuberculosis Mice chemistry.chemical_compound Bacterial Proteins Cell Wall Hydrolase Genetics medicine Animals Humans CoA salvage phosphopantetheinyl hydrolase chemistry.chemical_classification General Immunology and Microbiology Ecology biology Phosphoric Diester Hydrolases Cell Biology biology.organism_classification medicine.disease Lipids QR1-502 Mice Inbred C57BL carrier protein Acyl carrier protein Infectious Diseases Enzyme chemistry Pantetheine biology.protein Female dephosphopantetheinylation Phosphopantetheine Protein Processing Post-Translational Research Article |
| Zdroj: | Microbiology Spectrum, Vol 9, Iss 2 (2021) Microbiology Spectrum |
| ISSN: | 2165-0497 |
| Popis: | Phosphopantetheinyl hydrolase, PptH (Rv2795c), is a recently discovered enzyme from Mycobacterium tuberculosis that removes 4′-phosphopantetheine (Ppt) from holo-carrier proteins (CPs) and thereby opposes the action of phosphopantetheinyl transferases (PPTases). PptH is the first structurally characterized enzyme of the phosphopantetheinyl hydrolase family. However, conditions for optimal activity of PptH have not been defined, and only one substrate has been identified. Here, we provide biochemical characterization of PptH and demonstrate that the enzyme hydrolyzes Ppt in vitro from more than one M. tuberculosis holo-CP as well as holo-CPs from other organisms. PptH provided the only detectable activity in mycobacterial lysates that dephosphopantetheinylated acyl carrier protein M (AcpM), suggesting that PptH is the main Ppt hydrolase in M. tuberculosis. We could not detect a role for PptH in coenzyme A (CoA) salvage, and PptH was not required for virulence of M. tuberculosis during infection of mice. It remains to be determined why mycobacteria conserve a broadly acting phosphohydrolase that removes the Ppt prosthetic group from essential CPs. We speculate that the enzyme is critical for aspects of the life cycle of M. tuberculosis that are not routinely modeled. IMPORTANCE Tuberculosis (TB), caused by Mycobacterium tuberculosis, was the leading cause of death from an infectious disease before COVID, yet the in vivo essentiality and function of many of the protein-encoding genes expressed by M. tuberculosis are not known. We biochemically characterize M. tuberculosis’s phosphopantetheinyl hydrolase, PptH, a protein unique to mycobacteria that removes an essential posttranslational modification on proteins involved in synthesis of lipids important for the bacterium’s cell wall and virulence. We demonstrate that the enzyme has broad substrate specificity, but it does not appear to have a role in coenzyme A (CoA) salvage or virulence in a mouse model of TB. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|