A recent study led by Dr. Brad Pierce, an assistant professor of chemistry/biochemistry at the University of Texas at Arlington, examined an oxygen utilizing iron enzyme known as cysteine dioxygenase (CDO). This enzyme is found in high concentrations in heart, liver and brain tissue. Enzymes are proteins that act as catalysts to run metabolic functions, however sometimes these oxygen-dependent enzymes can produce highly toxic side products known as reactive oxygen species or ROS.
Pierce and colleagues discovered that mutations outside the CDO active site environment or “outer coordination sphere” have a profound effect on the release of ROS. Excess amounts of reactive oxygen species have been associated with many age-onset human diseases.
According to Pierce, “Most research in the past has focused on the active site inner coordination sphere of these enzymes, where the metal molecule is located. What we’re finding is that it’s really the second sphere that regulates the efficiency of the enzyme. In essence, these interactions hold everything together during catalysis. When this process breaks down, the enzyme ends up spitting out high levels of ROS and increasing the likelihood of disease.” Pierce feels that this discovery could be applied to other oxygen-dependent enzymes. CDO type enzymes make up about 20 percent of the enzymes in the human body. Pierce notes, “In principle, these findings could be extended to better understand how other enzymes within the class generate ROS and potentially be used to screen for genetic dispositions for ROS-related diseases.”
This research brings about a new level of detail to enzyme studies by using electron paramagnetic resonance (EPR). This technology is similar to magnetic resonance (MRI). Pierce was awarded a three-year, $300,000 grant from the National Science Foundation (NSF) in the fall of 2012 to study enzymes that are catalysts for the oxidation of sulfur-bearing molecules in the body.
Pamela Jansma, dean of the UT Arlington College of science, notes, “Dr. Pierce’s research is a good example of how basic science can set a path toward discoveries that affect human health. We look forward to his continued exploration of these findings”.
The Biochemistry article is titled “Second-Sphere Interactions between the C93-Y157 Cross-Link and the Substrate-Bound Fe Site Influence the O2 Coupling Efficiency in Mouse Cysteine Dioxygenase” and is accessible at: http://www.ncbi.nlm.nih.gov/pubmed/24279989.
Pierce is corresponding author and the study was published in December 2013 by the American Chemical Society journal Biochemistry. Co-authors include UT students Wei Li, Michael D. Pecore and Joshua K. Crowell. Co-author Elizabeth J. Blaesi is a graduate research assistant at the University of Wisconsin.
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