Fig. 6.

A proposed acid activation and proton conductance mechanism delineated by the D2–D4 models of the His37-Trp41 quartet. Hydrogen bonds involving the imidazole rings and between water molecules are indicated by dashed lines. At acidic pH, addition of a proton (cyan sphere) breaks an imidazole-imidazolium dimer and positions the previously shared proton (gray sphere) toward water below. Occasional opening of the Trp41 gate allows the release of the latter proton to the water chain underneath and the reformation of the imidazole-imidazolium dimer, now sharing the added proton.