Enzyme complex could be key to new cancer treatments

In these microscopic images of cells, the white areas indicate the presence of enzymes. The enzymes in images A and C are distributed throughout the cytoplasm because these cells... Click here for more information.

Penn State scientists are the first to observe in living cells a key step in the creation of adenine and guanine, two of the four building blocks that comprise DNA. Also called purines, the two building blocks are essential for cell replication. The findings, which will be published in the 4 April 2008 issue of the journal Science, could lead to new cancer treatments that prevent cancer cells from replicating by interfering with their abilities to make purines.

The group used cervical cancer cells--which have an increased demand for purines due to their rapid rates of replication--to demonstrate that a group of six enzymes is involved in the creation of purines. "Our research shows that these enzymes form a cluster prior to purine formation," said Erin Sheets, an assistant professor of chemistry and a collaborator on the project.

Although other researchers had, in the past, studied the enzymes individually in test tubes, no one, until now, had examined the group of enzymes together in living cells. "This is the first time that anyone has used the appropriate technology to look for this kind of complex in a living cell," said the team's leader Stephen Benkovic, Evan Pugh Professor of Chemistry and holder of the Eberly Family Chair in Chemistry.

These cells, which were grown in the absence of purines, contain enzymes that are labeled with fluorescent proteins. The bright areas represent enzyme clusters. Click here for more information.

Postdoctoral associates Songon An and Ravindra Kumar, from the Benkovic group, studied the enzyme clusters using a technique called fluorescence microscopy, in which fluorescent proteins are attached to molecules of interest and viewed under a special microscope. According to Sheets, the technique makes it easier to observe specific molecules in a cell. "It's like giving a bright orange helmet to your favorite football player so you can more easily monitor his actions," she said.