Transport mechanism of formate-nitrite transporters: The substrate anion, e.g., formate, is electrostatically attracted by a conserved lysine (blue shading) and slides into a hydrophobic vestibule. Substrate acidity decreases concomitantly with the lowering dielectricity, ε, facilitating proton transfer from the bulk water. The protonated, neutral substrate is largely preferred over the anion to pass the 2 lipophilic constriction sites (dark gray).