Docking simulation and activity test of PRL1 allosteric site

Abstract

Protein tyrosine phosphatases (PTPs) are important protein in cellular signal transduction which related with cell differentiation, transcription, metabolism and growth. Subfamily of the PTP, Phosphatases of regenerating liver (PRLs) which constitute small, prenylated in C-terminal are related to oncogenic and metastatic process. PRL1 is particularly contributed to the acquisition of metastatic property by promoting cell migration and invasion. So this phosphatase can be a potential therapeutic target. Conventionally, PTP inhibitors targeted the active site pocket which has limit of finding optimal compound with potency, selectivity and membrane permeability. Some PTPs has their own allosteric inhibition site which can provide an opportunity for development of new PTP therapeutics. Even though the allosteric site of PRL1 remains unknown, it can be helpful for new anticancer therapeutic agents. To predict allosteric sites of PRL1, i used Autodock Vina which simulates protein-chemical docking. I used 3 inhibitors to predict allosteric site simulation. By using result of simulation, i made mutated protein construct which is predicted allosteric residue mutated. After that, i did activity test of the protein. As a result of this activity test, I confirm that three residues are involved in the inhibition of this enzyme. I compared the results with the simulation results and confirm that the three residues mentioned above were associated with two allosteric sites, and consequently, we found two allosteric sites.