Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases

Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. 

Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.