Protein Phosphorylation is a reversible post-translational modification where-in, the terminal g-PO4 of ATP is transferred onto the surface of a target protein. Addition of a negative charge from the phosphate group changes the electrostatics of the substrate protein and directly alters its biological function. Protein phosphorylation events are positioned at the core of various cellular processes including cell division and differentiation.
Initially understood as the modest interplay between the opposing actions of Protein Kinases (that phosphorylate proteins) and Protein Phosphatases (that remove phosphates from proteins), this realm now includes phosphate-binding domains and the less-understood pseudo-enzyme forms of kinases and phosphatases. An intense interplay between these proteins and their allosteric regulation by small molecules, protein-protein interaction and post-translational modification maintains phosphorylation-based signaling.
Our laboratory focuses on the sequence, structural, dynamic and functional exploration of certain families of these proteins to advance the understanding of their mechanism and role in human disease. We harness a range of technologies for this purpose; including molecular biology, biochemical and biophysical techniques (circular dichroism, fluorescence polarization, surface plasmon resonance), enzymology, X-ray diffraction-based structural biology, molecular dynamics simulations, and amino-acid network analysis. A general research theme is the exploration of mechanistic signatures of regulation that influence the biological role of these proteins.