Enzyme complex could be key to new cancer treatments

The researchers attached fluorescent proteins to the enzymes of cells grown in the presence and absence of purines. They found that in the absence of purines, enzymes formed clusters at much higher rates, suggesting that they play a role in the creation of new purines. In contrast, cells also can produce purines by recycling old purine material. Owing to this salvage process, cells do not always need enzyme clusters; indeed, cluster formation was not observed in cells that were grown in the presence of purines. In a key experiment, the researchers were able to influence the association and dissociation of the enzyme cluster by changing the cells' exposure to purines.

Not all of the cells that were grown in the absence of purines contained enzyme clusters. "We think that the enzymes form clusters only when a cell needs purines, and that happens when a cell is required to replicate its DNA at a certain stage in its cell cycle," said Sheets. "Since each of our samples contain cells at different stages of the cell cycle, we did not expect all of them to be actively replicating their DNA. Therefore, we weren't surprised to find that some of our cells did not contain enzyme clusters."

Because purines are necessary for DNA replication and, ultimately, for cell replication, the ability to halt purine synthesis could prove to be a valuable method for treating cancer. "Cancer cells have very high demands for purines," said Benkovic. "If we can find a way to disrupt the formation of this particular enzyme cluster, it could become a potential new target for cancer therapy."

This research was supported, in part, through the Center for Optical Technologies at Penn State University, which receives support from the Commonwealth of Pennsylvania and the Donors of the American Chemical Society Petroleum Research Fund.

CONTACTS:
Erin Sheets: (+1) 814-863-0044,
Stephen Benkovic: (+1) 814-865-2882,
Barbara Kennedy (PIO): (+1) 814-863-4682,

IMAGES:
Images associated with this research are on the Web at http://www.science.psu.edu/alert/Sheets-Benkovic3-2008.htm