The investigation of the role of Protein Kinase K in signal transduction in Mycobacterium tuberculosis by molecular modelling approaches

Tuberculosis is a disease caused by the bacterium of Mycobacterium tuberculosis. The fact that the drugs in use have a history of more than 40 years and the elucidation of the drug resistance as well as the signal transmission processes and the mechanism are important for the discovery of new drugs. The current study has an objective to investigate the role of phosphorylation of Protein Kinase K (PknK), which is one of these 11 kinases, in the molecular recognition of its main substrate by molecular modelling approaches. First of all, because of the lack of 3D structures of PknK and VirS, the homology modelling was applied to have these structures for both proteins. The results indicated that the phosphorylation of corresponding threonine and serine has a significant impact on the recognition of VirS. Assisted Model Building with Energy Refinement (AMBER) was applied throughout the calculations. MD calculations as in periodic box for both proteins (PknK and VirS) design by homology modelling indicate that both models have been constitute in a good manner. Phosphorylation at Thr179, Thr181, Ser187 residues caused significant changes on the conformation of the protein which maybe the driving force in the recognation of VirS. The conformational changes indused by the phosphprylation of Ser252, Ser311, Thr327, Thr248 resiues in VirS. The binding to MymA operon.