sentence: The PMFs for PT from E148 in the central region to the extracellular solution with Cl either present or absent ( Figure 3 ) reveal that PT in this region occurs via a two-step process : ( 1 ) the change of the orientation of E148 side chain from the down to the up conformation and ( 2 ) the deprotonation of E148 in the up conformation followed by PT to the extracellular solution .