Oxidation of the Mycobacterium tuberculosis key virulence factor protein tyrosine phosphatase A (MptpA) reduces its phosphatase activity.
Anna NiesterukSridhar SreeramuluHendrik R A JonkerChristian RichterHarald SchwalbePublished in: FEBS letters (2022)
The Mycobacterium tuberculosis tyrosine-specific phosphatase MptpA and its cognate kinase PtkA are prospective targets for anti-tuberculosis drugs as they interact with the host defense response within the macrophages. Although both are structurally well-characterized, the functional mechanism regulating their activity remains poorly understood. Here, we investigate the effect of post-translational oxidation in regulating the function of MptpA. Treatment of MptpA with H 2 O 2 /NaHCO 3 , mimicking cellular oxidative stress conditions, leads to oxidation of the catalytic cysteine (C11) and to a conformational rearrangement of the phosphorylation loop (D-loop) by repositioning the conserved tyrosine 128 (Y128) and generating a temporarily inactive preclosed state of the phosphatase. Thus, the catalytic cysteine in the P-loop acts as a redox switch and regulates the phosphatase activity of MptpA.
Keyphrases
- mycobacterium tuberculosis
- protein kinase
- oxidative stress
- transcription factor
- hydrogen peroxide
- pulmonary tuberculosis
- escherichia coli
- staphylococcus aureus
- pseudomonas aeruginosa
- nitric oxide
- living cells
- single molecule
- ischemia reperfusion injury
- tyrosine kinase
- heat shock
- binding protein
- human immunodeficiency virus
- amino acid
- combination therapy