2.A.66.1.2
Drug:Na⁺ antiporter, VcmA (exports norfloxacin, ciprofloxacin, ofloxacin, daunomycin, doxorubicin, streptomycin, kanamycin, ethidium, 4',6'-diamidino-2-phenylindole, Hoechst 33342 and acriflavin). The 3-d x-ray structure (3.65Å resolution) is available (He et al., 2010). Ion binding and internal hydration have been studied by molecular dynamics simulations (Vanni et al., 2012).  NorM simultaneously couples drug export to the sodium-motive force and the proton-motive force. Residues involved and protein regions that play important roles in Na⁺ or H⁺ binding have been identified (Jin et al. 2014). Na⁺- and H⁺-driven conformational changes are facilitated by a network of polar residues in the N-terminal domain cavity, whereas conserved carboxylates buried in the C-terminal domain are critical for stabilizing the drug-bound state. These results establish the role of ion-coupled conformational dynamics in the functional cycle and implicate H⁺ in the doxorubicin release mechanism (Claxton et al. 2018).