In order to elucidate its function in apoptosis, researchers have created a model of proline dehydrogenase, an important cancer-preventing enzyme in the human body. Proline dehydrogenase enables the creation of superoxide, a highly reactive electron-rich oxygen species involved in the destruction of damaged cells. Using proline dehydrogenase from the bacteria Thermus thermophilus, which has been demonstrated to be functionally similar to the human version of the enzyme, the scientists used X-ray crystallography and bioninformatics to create a model.
“The three-dimensional model tells us a lot about the structure of the molecules and helps us understand how they work,” Tanner said. “This protein is important in cancer prevention because it enables the creation of superoxide, which aid in cell death. Cells aren’t meant to live forever, and at some point, they need to die and be destroyed. Cells that are damaged or diseased are usually destroyed in this process. Our structure tells us how oxygen gets access to electrons stored in the enzyme. We think we’ve identified a gate that opens to let oxygen into the enzyme where the electrons are stored.”
The researchers next aims to identify molecules that inactivate proline dehydrogenase and thus gain more insight in the anti-cancer abilities of this molecule.