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

ABSTRACT: 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. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-re

SUBMITTER: Nishida Y 

PROVIDER: S-EPMC9731990 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature