Recently identified protein group plays major role in nature

The Göttingen University team initially discovered the new protein switch -- known as a "NOS switch" because Nitrogen, Oxygen and Sulphur atoms are connected -- in a protein from the human pathogen Neisseria gonorrhoeae. However, the question remained whether this switch was widespread in nature. The researchers have now analyzed the entire database of known protein structures held in a publicly accessible repository for hitherto undetected NOS switches. The computational analysis by first author Dr Fabian Rabe von Pappenheim, University of Göttingen, produced hundreds of hits, which were then all individually analysed in detail. "Investigating these structures was an exciting endeavour. It was like travelling into the unknown for us," recalls Professor Kai Tittmann, University of Göttingen, who led the study.

The novel NOS switch was found to exist across all domains of life, and often at sites of proteins that are essential for biological function. Remarkably, numerous proteins from some of the most dangerous human pathogens have this switch, including a key enzyme from the SARS-CoV-2 coronavirus. In fact, this switch is a target for the recently approved antiviral drug for patients with mild to modrerate Covid-19 who might be at high risk of developing serious disease. In addition, the researchers discovered several new chemical forms of the NOS switch, which turns out to be a universally used regulation platform in biology. The identified proteins play central roles in almost every aspect of cellular activities, be it the expression of genes, signalling in and between cells, or metabolism.

"We believe that the discovery of these new protein switches will be a springboard for the development of a novel class of drugs that directly targets these switches," says Tittmann. "Many human proteins with known roles in severe diseases as well as proteins from bacteria and viruses are now known to be controlled by such switches. The newly identified switch is likely to play a central role in regulating their biological function as well."