Hahn explains that the mechanism of engineered allosteric regulation can be compared to the wheels on a car. A small part of each kinase molecule is key to its action within the cell. Attaching a protein engineered by Andrei Karginov to this part of the kinase causes the molecule to vibrate, keeping it from working well enough to control the cell just as loose bolts on a car wheel will keep the vehicle from moving forward effectively.
Scientists then use a drug to bind the engineered protein, tightening up the molecule and allowing the kinase to work normally like tightening the bolts on a car wheel.
"It's very precise. Just as you can map which switch in the circuit box in your home controls specific lights and appliances, this mechanism controls specific kinases, allowing researchers to trace their action precisely within the cell," Hahn says.
Hahn predicts that the new technique will enable faster, less expensive study of cell signaling pathways implicated in cancer as well as a large range of human diseases and disorders.
Hahn points out that this was a highly collaborative effort, made possible only by combining the skills of UNC researchers from diverse disciplines. The research team from UNC includes molecular biologist Andrei V. Karginov, PhD, Research Assistant Professor of Pharmacology, and computational biologists Feng Ding, Research Assistant Professor of Pharmacology, Pradeep Kota, a graduate student in biochemistry and biophysics, and Nikolay V. Dokholyan, PhD, Associate Professor of Biochemistry and Biophysics.
|Contact: Ellen de Graffenreid|
University of North Carolina School of Medicine