Quinone binding site of the cytochrome bc1 complex (Qo site)

The quinone binding site of the cytochrome bc1 complex (Complex III) in Neisseria gonorrhoeae is a critical component of the bacterial respiratory chain, facilitating the transfer of electrons from ubiquinol to cytochrome c. This process, known as the Q-cycle, involves two distinct catalytic sites: the quinol oxidation (Qo) site and the quinone reduction (Qi) site, both located within the cytochrome b subunit. In N. gonorrhoeae, this complex is essential for maintaining the proton motive force required for ATP synthesis and supporting growth under the microaerobic and anaerobic conditions encountered during infection. Recent research has identified the Qo site as a highly selective therapeutic target for treating multidrug-resistant gonorrhea. Small molecules such as 2-nonyl-4-quinolone N-oxide (NQNO) and its derivatives competitively inhibit this site, leading to rapid ATP depletion and the activation of endogenous toxin-antitoxin systems, such as the Zeta1 toxin, which results in bacterial cell death. Importantly, these inhibitors can demonstrate high selectivity for the gonococcal enzyme over human mitochondrial counterparts, offering a path for narrow-spectrum antibiotic development.

Other names

Qo siteQp siteQuinol oxidation siteUbiquinol oxidation siteQi siteQn siteComplex III quinone binding siteQuinol-binding site of cytochrome bc1

Inhibition of electron transfer by competitively blocking the quinol oxidation (Qo) site of the cytochrome bc1 complex, which disrupts the Q-cycle, halts the respiratory chain, and induces lethal oxidative stress and toxin release.