Rogue Enzyme

Recent findings uncover an agent of inflammation.

Our immune systems rely on white blood cells to create enzymes that fight disease. But sometimes these enzymes go too far, attacking tissue and creating inflammation that can lead to obstructive pulmonary disease, cancer, heart disease and other serious maladies.

A recent finding by Steven Van Doren, an MU biochemistry professor, is an important first step in helping scientists understand what’s going wrong. In an NIH-funded study published in Nature Communications, Van Doren determined that one of the enzymes implicated in inflammation, MMP12, does not, as scientists previously supposed, remain outside of cells while it fights infections. Instead, it often lands on the surface of cells and then travels to their centers.

“Now that we know the MMP12 enzyme can bind to cells and travel all the way to the nucleus at the center of a cell, we can begin further study of how this enzyme interacts with those cells.” The finding, he says, will advance efforts aimed at creating therapies that can turn off MMP12 and other inflammation-related enzymes.

Van Doren’s laboratory used nuclear magnetic resonance spectroscopy to measure the orientations of the MMP12 molecules on membranes that mimic cell surfaces. They then used a fluorescent substance to track the movements of MMP12 throughout living cells. “We know that MMP12 enzymes play important roles in fighting bacterial and viral infections and fighting arthritis,” Van Doren says. “The more we understand these enzymes, the closer we come to learning how to use these enzymes more effectively to fight diseases while preventing them from causing damage when they act inappropriately. This illustrates the importance of basic scientific research when looking to solve large, practical problems.”

Status Envy Art by Ross MacDonald

Understanding the behavior of MMP12, an enzyme created by white blood cells, could yield treatments for several inflammation-related illnesses.

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