Fig. 5. Proposed mechanism of transport by EmrE. This schematic depicts a possible catalytic cycle for TPP⁺/H⁺ binding and release from the EmrE transporter. As the substrate approaches the hydrophobic binding pocket, two protons are released from the negatively charged glutamate triplet. The positively charged substrate is bound through electrostatic interactions with the negatively charged carboxylate groups extending from each glutamate residue. Following an unknown conformational transition, the opening to the binding pockets becomes accessible to the alternative face of the membrane, while being closed off from the opposite face. The subsequent movement of two protons towards the binding pocket catalyzes the release of the bound substrate. The transporter then relaxes, undergoing a conformational transition that converts the binding pocket accessibility back to the original membrane face.