Structural Biochemistry/Kinase/Cyclin-Dependent Kinase

Cyclin-dependent kinases (CDKs) are protein kinases that regulate the cell cycle, transcription, and processing of mRNA. In order for them to function at all, these kinases bind to proteins called cyclins. These kinases phosphorylate their substrates on serines and threonines.

Evolution

Research has shown that cyclin-dependent kinases can be found throughout all eukaryotic cells. This was found by substituting human cyclin-dependent kinases into the corresponding kinases in yeast. Although it seemed doubtful due to the long evolution divergence between humans and yeast, it was found that yeast colonies still grew after promoting a human library into fission yeast and many transformations. The growth of these colonies greatly showed that the cell cycle was regulated the same way in human cells and in yeast, and thus all eukaryotic cells as well. This also led to show that model organisms, such as yeast, can be used to study issues in humans, such as diseases.

CDK2

Cyclin-dependent kinase 2 are kinases found in homo sapiens (humans).

Functions

Cyclin-dependent kinase 2 is regulated by cyclin E and cyclin A and only functions during the G1-S phase of the cell cycle. It is important for the G1/S transition in that cyclin E binds to CDK2, which is needed for when G1 transitions to the S phase, while cyclin A then binds to CDK2 to complete the transition.

Structure

Solving this kinase’s structure in 1993 showed that the activation site slightly blocks the binding site for ATP. Kinases typically have two lobes, and in this particular structure, the two lobes were in a closed conformation, and its C-helix was in the wrong direction that encourages binding with the triphosphate segment of ATP.

Reference

"Structural Basis for Control by Phosphorylation." Chemical Reviews. 06 Dec. 2012. Web. 06 Dec. 2012. <http://pubs.acs.org/doi/full/10.1021/cr000225s>
"Finding CDK: Linking yeast with humans." Nature Cell Biology. 06 Dec. 2012. Web. 06 Dec. 2012. <http://www.nature.com/ncb/journal/v14/n8/full/ncb2547.html>