title: Tetraethylammonium binding to the outer mouth of the KcsA potassium channel: implications for ion permeation.
abstract: Extracellular tetraethylammonium (TEA+) inhibits the current carried out by K+ ions in potassium channels. Structural models of wild-type (WT) and Y82C KcsA K+ channel/TEA+ complexes are here built using docking procedures, electrostatics calculations and molecular dynamics simulations. The calculations are based on the structure determined by Doyle et al. (11) Our calculations suggest that in WT, the TEA+ cation turns binds at the outer mouth of the selectivity filter, stabilized by electrostatic and hydrophobic interactions with the four Tyr82 side chains. Replacement of Tyr82 with Cys causes a decrease of the affinity of the cation for the channel, consistently with the available site-directed mutagenesis data (16). An MD simulation in which K+ replaces TEA+ provides evidence that TEA+ binding site can accommodate a potassium ion, in agreement with the high-resolution structure recently reported by Zhou et al. (20)
authors.affiliation: INFM-Democritos Center for Molecular Simulations and International School for Advanced Studies (SISSA), Via Beirut 4, 1-34014 Trieste, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guidoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D005110:Extracellular Space / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013302:Streptomyces; D019789:Tetraethylammonium / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D014443:Tyrosine; D019789:Tetraethylammonium; D011188:Potassium