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A novel binding pocket of cyclin-dependent kinase 2.

ABSTRACT: 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.

SUBMITTER: Chen H

PROVIDER: S-EPMC4497517 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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A novel binding pocket of cyclin-dependent kinase 2.

Chen Hao H Van Duyne Rachel R Zhang Naigong N Kashanchi Fatah F Zeng Chen C

Proteins 20090101 1

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 ...[more]

PMID: 18615713

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