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!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy