Brad Pierce, an assistant professor of chemistry/biochemistry at The University of Texas at Arlington, recently led a team that examined an oxygen utilizing iron enzyme called cysteine dioxygenase or CDO, which is found in high levels within heart, liver, and brain tissues.
First and Second coordination spheres of the CDO active site.
Enzymes are proteins that act as catalysts to enable metabolic functions, but under some circumstances these oxygen-dependent enzymes can also produce highly toxic side products called reactive oxygen species or ROS.
For the first time, Pierce’s team found that mutations outside the CDO active site environment or “outer coordination sphere” have a profound influence on the release of ROS. Excess ROS has been linked to numerous age-onset human disease states.
“Most research in the past has focused on the active site inner coordination sphere of these enzymes, where the metal molecule is located,” said Pierce. “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.”
The study was published in December by the American Chemical Society journal Biochemistry. Pierce is corresponding author on the paper, with UT Arlington students Wei Li, Michael D. Pecore and Joshua K. Crowell as co-authors. Co-author Elizabeth J. Blaesi is a graduate research assistant at the University of Wisconsin.
Pierce believes the findings from the CDO enzyme could be applied to other oxygen-dependent enzymes, which make up about 20 percent of the enzymes in the human body.
“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,” he said.
Pierce’s research brings a new level of detail to enzyme study through the use of electron paramagnetic resonance or EPR, a technology similar to the magnetic resonance imaging or MRI used in the medical field. In fall 2012, the National Science Foundation awarded Pierce a three-year, $300,000 grant to study enzymes that are catalysts for the oxidation of sulfur-bearing molecules in the body.
“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,” said Pamela Jansma, dean of the UT Arlington College of Science.
The title of the Biochemistry paper is “Second-Sphere Interactions between the C93-Y157 Cross-Link and the Substrate-Bound Fe Site Influence the O2 Coupling Efficiency in Mouse Cysteine Dioxygenase.” It is available online here: http://www.ncbi.nlm.nih.gov/pubmed/24279989.The University of Texas at Arlington is a comprehensive research institution of more than 33,300 students and 2,300 faculty members in the epicenter of North Texas. It is the second largest institution in The University of Texas System. Total research expenditures reached almost $78 million last year. Visit www.uta.edu to learn more.
Traci Peterson | EurekAlert!
MACC1 Gene Is an Independent Prognostic Biomarker for Survival in Klatskin Tumor Patients
31.08.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
01.09.2015 | Press release
01.09.2015 | Materials Sciences
01.09.2015 | Materials Sciences