Terminal oxidase

Terminal oxidases are essential enzymes located at the end of the aerobic respiratory electron transport chain in both prokaryotic and eukaryotic organisms (Borisov et al., 2011, PubMed: 21439010). Their primary biological function is to catalyze the four-electron reduction of molecular oxygen to water, a process that is coupled to the translocation of protons across the cytoplasmic or inner mitochondrial membrane (Spero et al., 2015, PubMed: 26296005). This proton translocation generates an electrochemical gradient, known as the proton motive force, which is utilized by ATP synthase to produce cellular energy in the form of ATP (Cook et al., 2014, PubMed: 24108122). In humans, this role is fulfilled by cytochrome c oxidase (Complex IV), while bacteria often possess multiple, structurally distinct terminal oxidases like cytochrome bd and cytochrome bo3 to survive in diverse environments (Thesseling et al., 2019, PubMed: 31110256). Because of their critical role in bioenergetics, bacterial terminal oxidases have emerged as promising therapeutic targets for treating infections, particularly multi-drug resistant tuberculosis (Pethe et al., 2013, PubMed: 23913171). Drugs targeting these enzymes aim to disrupt the pathogen's energy supply, leading to growth inhibition or cell death, though selectivity must be maintained to avoid inhibiting human mitochondrial respiration (Lu et al., 2015, PubMed: 26150517). Research in this area focuses on identifying small molecules that can selectively bind to unique bacterial oxidase sites, such as the oxygen-binding pocket of cytochrome bd, to provide potent and specific antimicrobial activity.

Other names

Cytochrome c oxidaseCytochrome bd oxidaseCytochrome bo3 oxidaseComplex IVQuinol oxidaseFerrocytochrome c:oxygen oxidoreductase

Inhibition of the final step of the electron transport chain by preventing the reduction of molecular oxygen to water, thereby disrupting the proton motive force and ATP production (Borisov et al., 2011, PubMed: 21439010).