A novel binding pocket of cyclin-dependent kinase 2.

The cyclin-dependent kinase 2 (cdk2) is a serine/threonine protein kinase that plays a key role in the cell cycle control system of all eukaryotic organisms. It has been a much studied drug target for potential anticancer therapy. Most cdk2 inhibitors in clinical development target almost exclusively the catalytic ATP-binding pocket of cdk2. However, several five amino-acid peptide inhibitors that are directed towards a noncatalytic binding pocket of cdk2 are reported here. Upon binding to this new pocket located at the cdk2 and cyclin interface, these peptide inhibitors are found to disrupt the cdk2/cyclin E complex partially and diminish its kinase activity in vitro.