Gayan Wijeratne, assistant professor of chemistry and recent recipient of a Maximizing Investigators’ Research Award (MIRA) from the National Institute of Health, is developing new ways to mimic the proteins vital to life.
Wijeratne, who moved to the UA chemistry department from the University of Alabama at Birmingham in 2023, is currently studying the fundamental biological processes that create energy in animals and plants.
Wijeratne said aerobic enzymes, which are proteins that speed up reactions involving oxygen, are very involved in all aerobic organisms, including humans. For example, cellular respiration, which is how energy is made in the human body, uses aerobic enzymes.
While understanding these proteins helps scientists understand how energy is created in plants and animals, it is also tied very closely to human health. Wijeratne’s work with metal-containing enzymes that activate nitrogen oxide molecules was recognized with the NIH award in June, which will continue to fund his work synthesizing new stable enzymes that can clarify how the enzymes in humans function on a deeper level.
For example, these enzymes activate nitric oxide molecules.
“Nitric oxide gasses are involved in vasodilation, which is very important in regulating blood pressure,” said Shanuk Rajapakse, a graduate student in Wijeratne’s lab.
Currently metalloenzymes, or enzymes containing metallic components, are being studied as a means of transport for medication used to fight cancer, COVID-19, neurodegenerative diseases, autoimmune diseases and more.
“People are constantly trying to find better drugs for this,” Wijeratne said. “But the possibilities are limited because we don’t know how they operate.”
On the other hand, the aerobic enzymes that the metalloenzymes mimic are important players in the progression of these diseases. Further research of how these proteins work can help researchers know why these proteins occasionally make mistakes in the human body, which can lead to these diseases.
However, studying these enzymes isn’t so simple..
“It’s difficult because these proteins are very sensitive,” Wijeratne said of the proteins’ instability in nature.
To overcome this hurdle, scientists develop proteins inspired by nature that behave similarly to the enzymes they want to study. Metalloenzymes are currently a focus in this field. These enzymes facilitate similar reactions to aerobic enzymes but are much more stable in nature.
By analyzing how these model enzymes react in different environments, Wijeratne is able to understand how similarly constructed aerobic enzymes behave.
In the lab, this looks like synthesizing metalloenzymes and then testing their properties.
“After we have the right models, we try to find out what kind of reaction we have access to,” said Samith Dewage, a Ph.D. student in the lab. “From that, we get a basic idea of whether and how we can find out how our system behaves.”
Once the model enzymes are made, the lab uses advanced instruments that use light to give information about the basic features of proteins. The results are analyzed to understand how the proteins move or react to their environment.
To focus on the specific proteins they care about, the lab performs these tests in a cryogenic setup. This cools the samples down to a temperature far below freezing, which limits how the proteins can move and interact while researchers are taking measurements.
Wijeratne is pushing forward the overall understanding of these kinds of proteins.
“Our model systems will help people understand the mechanism, and that way we can come up with better drug candidates than what are available,” Wijeratne said.
