Boffins create 3-D model of cancer-preventing enzyme for study

Scientists at the University of Missouri (MU) have created a three-dimensional model of cancer-preventing enzyme Proline dehydrogenase to study how the protein works.

Washington, May 12 : Scientists at the University of Missouri (MU) have created a three-dimensional model of cancer-preventing enzyme Proline dehydrogenase to study how the protein works.

It is well known that Prolien dehydrogenase plays a very significant role in apoptosis, the process of cell death, by enabling the creation of a highly reactive electron-rich oxygen species called superoxide.

Professor John J. Tanner and doctoral student Tommi A. White say that their model has revealed the process by which proline dehydrogenase creates superoxides. They say that for the purpose, the protein "opens up to allow oxygen to 'steal' electrons".

As the human form of proline dehydrogenase is difficult to work with, the scientists studied it from the bacteria Thermus thermophilus. They involved bioinformatics and biochemical studies in their project so as to ensure that the enzyme is functionally similar to its human version.

The researchers used X-ray crystallography and biochemical analysis to create the model of proline dehydrogenase, which they believe can tell them more about the molecule's structure and functions.

"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," he added.

White said that it was unusual for proline dehydrogenase to be involved in such a process because the usual job of that type of enzyme is to transfer electrons to the mitochondrial membrane, and disallow them to be attached to oxygen to create highly reactive superoxides.

Both Tanner and White hope to continue to study proline dehydrogenase and the molecules that can inactivate it. They are also planning to examine another protein that presumably works in collaboration with proline dehydrogenase, so that they may understand how that protein affects the cancer-preventing abilities of the enzyme.

ANI