2.A.1.3.4
(Mono- and divalent organocation):H⁺ antiporter. Transmembrane helix 12 of QacA lines the bivalent cationic drug binding pocket (Hassan et al., 2007). Two sites, D34 and D411 are involved in substrate recognition, while E407 facilitates substrate efflux as a protonation site and plays a role as a substrate recognition site for the transport of dequalinium, a divalent quaternary ammonium compound (Majumder et al. 2019). TMS 12 and its external flanking loop are required for the structural and functional integrity of QacA, and they contain amino acids directly involved in their interactions with substrates (Dashtbani-Roozbehani et al. 2023). Cryo-EM structures of QacA from S. aureus revealed a novel extracellular loop with an allosteric role (Majumder et al. 2023).