Research enlivens the role of so-called ‘dead’ enzymes

Bioinformatics doctoral candidate Annie Kwon, working with UGA professor Natarajan Kannan and a team of researchers, is first author on a recent paper revealing that a class of enzymes previously thought to be useless is prevalent across all domains of life in fact serves an important purpose in cell communications:

The study, published in Science Signaling, evolved from Kwon’s research trip to the University of Liverpool, where she worked with Patrick Eyers, a longtime collaborator with the Kannan lab. Kwon was one of the first students to receive a fellowship through the UGA-University of Liverpool graduate exchange program, which funded her trip in April 2018.

The project grew out of conversations between Kannan and Eyers, the result of inter-institutional collaborations made possible through the UGA-University of Liverpool Pump-Priming Grant Program.

“Patrick is the pseudokinase expert, and after talking with him, we realized that there’s a big gap in the pseudokinase field,” Kwon said. “Some of them are really well studied in humans, but no one’s really looked for them in other organisms. Just from an initial look, we found that they’re common in other organisms—especially in bacteria, which was unexpected.”

Finding so many pseudokinase sequences in bacteria led the team to keep looking, and the study became much more comprehensive. Eventually they classified nearly 30,000 eukaryotic, 1,500 bacterial and 20 archaeal pseudokinase sequences into 86 families, including about 30 families that were previously unknown. 

“Our study was the first to show that pseudokinases are prevalent across diverse species and are well represented in plants and fungi,” said Kannan, associate professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences. 

Protein kinases are a class of enzymes involved in a range of diseases, particularly in cancer. They turn signals on and off in cells—a critical part of how cells communicate with each other. Pseudokinases are related proteins that lack the machinery needed to generate on and off signaling, and for many years they were considered to be evolutionary leftovers and ignored.

Teams of people teaching as they train and push new research frontiers is the dynamic of success at UGA, one that draws talented people to campus and addresses scientific challenges. Congratulations to Dr. Kwon, Dr. Kannan and their colleagues on this important publication on a vital research front.