Technologists are using the Canadian Light Source at the University of Saskatchewan to study how enzymes found in all forms of life (ribonucleases) can be modified to work to humanity’s advantage.
The Canadian Light Source houses 22 synchrotron beamlines and an electron beamline, supporting a wide variety of research applications.
This technology could have wide-ranging applications, from better cancer treatments and more effective pharmaceuticals, to more efficient and environmentally friendly industrial catalysts.
In the human body there are eight active ribonucleases (RNases). Ribonucleases are essential participants in almost every aspect of RNA metabolism including RNA maturation, RNA degradation and turnover, RNA quality control, and even as mediators of regulation.
These enzymes are secreted by a large variety of different tissues and help manage the messages that come from our DNA. These enzymes are nearly identical in terms of their 3D architecture and molecular makeup, yet they carry out very different functions. For example, some protect people from infections while others contribute to tumour growth.
Professor Nicolas Doucet at the Institut National de la Recherche Scientifique’s Armand-Frappier Santé Biotechnologie Research Centre has been studying how to differentiate and modify these enzymes.
He had previously discovered that the function of a ribonuclease could be identified by its movements at the molecular level. Now, they have found a way to hack them too.
“By reconstructing the evolutionary ancestor of two enzymes, it allowed us to figure out how mutations have occurred but also how they’ve influenced specific biological functions throughout evolution,” explains Doucet. “This provided us with a tool to effectively predict how to transform the activity of an enzyme.”
His team successfully modified an enzyme so that it became antibacterial and toxic to cells (cytotoxic). By using the beamlines at the CLS, this enabled the scientists to analyse enzymes and proteins at an atomic scale.
This work provides a means to better design inhibitors in the context of drug design or pharmaceutical applications and to design or modify biocatalysts for targeted, specific industrial applications.
The findings suggest that engineering our genetics is possible and this could bring about advances in medicine and industry.
The research appears in the Journal of Biological Chemistry, titled “Ancestral sequence reconstruction dissects structural and functional differences among eosinophil ribonucleases.”
