Protein kinases are enzymes that play a key role in the initiation and control of cell signaling. They use a chemical mechanism known as phosphotransfer or phosphorylation to transfer the terminal phosphates of ATP to the Ser/Thr/Tyr/His amino acids of target proteins. Phosphorylation changes the function, location, and interactions of a target protein with other cellular proteins. Cell development, metabolism, immunological response, and neural signaling are all regulated by phosphorylation events.

There are about 518 different protein kinases in the human genome. Each one has its preferred substrates and ways of regulation, but they all share a conserved catalytic domain. Well-studied kinases include Growth Factor Receptors like EGFR, IR, FGFR, Cyclic-AMP dependent Protein Kinase A (PKA), and mitogen-activated protein kinases (MAPKs) that regulate cell proliferation. Protein kinase mutations and aberrations have been linked to several human diseases, including diabetes, neurodegeneration, and cancer, due to their crucial function in signaling. Protein kinases are, predictably, among the most attractive targets for pharmaceutical intervention. Our team investigates the allosteric foundations of kinase activity and how their structure and intrinsic dynamics may be used to manipulate their functional properties.

Protein tyrosine phosphatases (PTPs) are enzymes that hydrolyze phosphates from the phospho-tyrosine residues of target proteins. In this sense, their function appears to be a straightforward reversal of protein kinase functioning; nevertheless, cellular signaling is more sophisticated and complex. Not all tyrosine phosphorylations are the same in function; some are activating, while others are deactivating modifications. As a result, depending on the cellular/signaling context, their elimination is either deactivating or activating. PTPs play a vital function in protein phosphorylation homeostasis regulation; however, they were formerly considered basic housekeeping proteins. Growing scientific evidence suggests that abnormal PTP expression or activity results in human illnesses such as cancer, diabetes, cardiovascular, autoimmune, and neuropsychiatric disorders.

PTPs are interesting drug targets, but it is hard to make protein-specific drugs because their catalytic domain, mechanism, and active site chemistry are all the same. Our team studies the structure, dynamics, and allosteric properties based on the dynamics of these proteins to find mechanics that are unique to these proteins and that might make them easier to target for therapy. To better leverage the protein chemistry of PTPs, we also strive to understand their protein-specific regulation processes.