UC San Diego

Protein Tyrosine Phosphatases (PTPs) are drug target candidates due to their role in cell signaling and involvement in the pathologies of various diseases. Difficulty in developing orthosteric inhibitors of PTPs has raised interest in the development of allosteric inhibitors. Previous studies have identified an allosteric mechanism in receptor-type protein tyrosine phosphatase α (RPTPα), yet the mechanism requires further characterization for future development of small molecule therapeutics. In this study, through comparing RPTPα and the closely related RPTPε, we achieved the identification and in vitro validation of a segment of RPTPα (residues 261-330) responsible for its allosteric effect. It lays the groundwork for identification of amino acid residues participating in the establishment of allostery, which is a step in fully elucidating the allosteric mechanism.