A distinctive feature of prokaryotic Na+-channels is the presence of four glutamate residues in their selectivity filter. In this study, how the structure of the selectivity filter, and the free-energy profile of permeating Na+ ions are altered by the protonation state of Glu177 are analyzed. It was found that protonation of a single glutamate residue was enough to modify the conformation of the selectivity filter and its conduction properties. Molecular dynamics simulations revealed that Glu177 residues may adopt two conformations, with the side chain directed toward the extracellular entrance of the channel or the intracellular cavity. The likelihood of the inwardly directed arrangement increases when Glu177 residues are protonated. The presence of one glutamate residue with its chain directed toward the intracellular cavity increases the energy barrier for translocation of Na+ ions. These higher-energy barriers preclude Na+ ions to permeate the selectivity filter of prokaryotic Na+-channels when one or more Glu177 residues are protonated.
- GATED SODIUM-CHANNEL, MOLECULAR-DYNAMICS SIMULATIONS, CRYSTAL-STRUCTURE, ION CONDUCTION, K+ CHANNEL, SELECTIVITY, PERMEATION, CONFORMATION, NA(V)AB, NACHBAC