Key Residues in Mycobacterium tuberculosis Protein Kinase G Play a Role in Regulating Kinase Activity and Survival in the Host

摘要: Protein kinase G (PknG) in Mycobacterium tuberculosis has been shown to modulate phagosome-lysosome fusion. The protein three distinct domains, an N-terminal Trx domain, a and C-terminal TPR domain. present study extensively analyzes the roles of these domains regulating PknG activity function. We find that domain by itself is inactive, signifying importance flanking domains. Although deletion severely impacts protein, region also contributes significantly kinase. Apart from this, dependent on presence threonine 309 p + 1 loop activation segment. Mutating conserved cysteine residues motifs makes refractory changes redox environment. In vitro experiments identify 63 as major phosphorylation site protein. Importantly, we this only phosphorylated vivo. Macrophage infection studies reveal first 73 residues, motifs, residue are independently essential for modulating PknG-mediated survival mycobacteria its host. have extended investigate role mutants pathogenesis mice. Our results reinforce findings macrophage experiments, time demonstrate expression non-pathogenic allows continued existence bacteria host tissues.