Oxidative unfolding of the rubredoxin domain and the natively disordered N-terminal region regulate the catalytic activity of Mycobacterium tuberculosis protein kinase G was written by Wittwer, Matthias;Luo, Qi;Kaila, Ville R. I.;Dames, Sonja A.. And the article was included in Journal of Biological Chemistry in 2016.Electric Literature of C13H16N2O2S This article mentions the following:
Mycobacterium tuberculosis escapes killing in human macrophages by secreting protein kinase G (PknG). PknG intercepts host signaling to prevent fusion of the phagosome engulfing the mycobacteria with the lysosome and, thus, their degradation The N-terminal NORS (no regulatory secondary structure) region of PknG (approx. residues 1-75) has been shown to play a role in PknG regulation by (auto)phosphorylation, whereas the following rubredoxin-like metal-binding motif (RD, residues ∼74-147) has been shown to interact tightly with the subsequent catalytic domain (approx. residues 148-420) to mediate its redox regulation. Deletions or mutations in NORS or the redox-sensitive RD significantly decrease PknG survival function. Based on combined NMR spectroscopy, in vitro kinase assay, and mol. dynamics simulation data, we provide novel insights into the regulatory roles of the N-terminal regions. The NORS region is indeed natively disordered and rather dynamic. Consistent with most earlier data, autophosphorylation occurs in our assays only when the NORS region is present and, thus, in the NORS region. Phosphorylation of it results only in local conformational changes and does not induce interactions with the subsequent RD. Although the reduced, metal-bound RD makes tight interactions with the following catalytic domain in the published crystal structures, it can also fold in its absence. Our data further suggest that oxidation-induced unfolding of the RD regulates substrate access to the catalytic domain and, thereby, PknG function under different redox conditions, e.g. when exposed to increased levels of reactive oxidative species in host macrophages. In the experiment, the researchers used many compounds, for example, Ax20017 (cas: 329221-38-7Electric Literature of C13H16N2O2S).
Ax20017 (cas: 329221-38-7) belongs to benzothiophene derivatives. Benzothiophene is relatively a stable molecule. The electrophilic substitution of benzothiophene systems is much less regioselective than that of indoles. Due to its aromaticity, thiophenes do not exhibit the same properties as conventional thioethers.Electric Literature of C13H16N2O2S
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem