The domain architecture of PtkA, the first tyrosine kinase from , differs from the conventional kinase architecture.

The discovery that MptpA (low-molecular-weight protein tyrosine phosphatase A) from () has an essential role for virulence has motivated research of tyrosine-specific phosphorylation in and other pathogenic bacteria. The phosphatase activity of MptpA is regulated via phosphorylation on Tyr and Tyr Thus far, only a single tyrosine-specific kinase, protein-tyrosine kinase A (PtkA), encoded by the gene has been identified within the genome. MptpA undergoes phosphorylation by PtkA. PtkA is an atypical bacterial tyrosine kinase, as its sequence differs from the sequence consensus within this family. The lack of structural information on PtkA hampers the detailed characterization of the MptpA-PtkA interaction. Here, using NMR spectroscopy, we provide a detailed structural characterization of the PtkA architecture and describe its intra- and intermolecular interactions with MptpA. We found that PtkA's domain architecture differs from the conventional kinase architecture and is composed of two domains, the N-terminal highly flexible intrinsically disordered domain (IDD) and the C-terminal rigid kinase core domain (KCD). The interaction between the two domains, together with the structural model of the complex proposed in this study, reveal that the IDD is unstructured and highly dynamic, allowing for a "fly-casting-like" mechanism of transient interactions with the rigid KCD This interaction modulates the accessibility of the KCD active site. In general, the structural and functional knowledge of PtkA gained in this study is crucial for understanding the MptpA-PtkA interactions, the catalytic mechanism, and the role of the kinase-phosphatase regulatory system in virulence.