Structural characterization of the intrinsically disordered domain of Mycobacterium tuberculosis protein tyrosine kinase A

Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDD P tkA ) of unknown function, located N-terminally to the well-folded kinase core domain. Here, we characterize the conformation of IDD P tkA under varying biophysical conditions and phosphorylation using NMR-spectroscopy. Our results confirm that the N-terminal domain of PtkA exists as an IDD at physiological pH. Furthermore, phosphorylation of IDD P tkA increases the activity of PtkA. Our findings will complement future approaches in understanding molecular mechanisms of key proteins in pathogenic virulence.