Exploring the Binding Sites of Glycogen Synthase Kinase 3. Identification and Characterization of Allosteric Modulation Cavities

This paper reported the discovery of seven different binding pockets in the surface of the protein glycogen synthase kinase 3 (GSK-3). The activity of GSK-3 is really important for life, however its overactivity has been associated with a lot of unmet diseases. Especially for Alzheimer's disease, the overexpression of GSK-3 has a central role in the development of the neuropathological defects. Using the fpocket and hpocket programs, they found four new pockets that are located on the surface of the protein and that do not interact with ATP binding. They wanted to discover allosteric binding pockets to be able to target only the aberrant overactivity of GSK-3.

I found this was an interesting paper. In class we saw different classes of protein kinase inhibitors which could target different conformations of the protein. The inhibitors could either target the inactive or active form of the protein to make the protein inactive. Here the authors looked for druggable cavities on the surface of the protein to develop a non-ATP competitive inhibitor and only target abnormal overexpression of GSK-3.