Exploring quinone-binding sites as targets for pesticides

Quinones, such as ubiquinone and plastoquinone, are essential components of most photosynthetic and respiratory electron transfer chains. Proteins with quinone-binding sites (Q-sites) regulate the oxidation and reduction of these molecules that mediate processes vital for sustaining life. Due to their function as mobile electron carriers, quinones bind relatively weakly at Q-sites, making them vulnerable to disruption by potent inhibitors that interfere with essential biological functions. As a result, Q-sites have emerged as key targets for numerous pesticides. Advances in X-ray crystallography and cryo-electron microscopy have revealed detailed structural insights into Q-sites across a variety of proteins. While Q-sites universally recognize quinones, their geometric and electronic configurations differ among proteins. These variations have supported the development of highly specific pesticides but have also enabled resistance through target-site mutations that hinder pesticide binding. This review explores the unique features of individual Q-site and the mechanisms of resistance linked to them. Additionally, we examine the physical properties of pesticides that interact with membrane-embedded Q-sites and compare the structural characteristics of these binding pockets. © 2025 Society of Chemical Industry.