Structural Studies of the Complex Between Akt-in and the Akt2-PH Domain Suggest that the Peptide Acts as an Allosteric Inhibitor of the Akt Kinase

Serine/threonine kinase Akt plays a central role in the regulation of cell survival and proliferation. Hence, the search for Akt specific inhibitors constitutes an attractive strategy for anticancer therapy. We have previously demonstrated that the proto-oncogene TCL1 coactivates Akt upon binding to its Plekstrin Homology Domain, and we proposed a model for the structure of the complex TCL1:Akt2-PHD. This model led to the rational design of Akt-in, a peptide inhibitor spanning the A -strand of human TCL1 that binds Akt2 PH domain and inhibits the kinase activation.