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.
Chen
Hao
H
Department of Physics, The George Washington University, Washington, District of Columbia 20052, USA.
Van Duyne
Rachel
R
Zhang
Naigong
N
Kashanchi
Fatah
F
Zeng
Chen
C
D001665:Binding Sites; D003198:Computer Simulation; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding
D019927:Cyclin E; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2