Genetics of acquired long QT syndrome
J. Clin. Invest. Dan M. Roden, et al. 115:2025 doi:10.1172/JCI25539 [Go to this article.]

Figure 3
Hypothesized molecular structure of the drug-binding site in the HERG channel. (A) The orientation of the channel pore, lined by S6 helices, is shown; drug access is via the intracellular face of the channel. Portions of 2 of the 4 subunits of the homotetrameric channel are shown, and the other 2 are omitted for clarity. The aromatic residues (tyrosine [Tyr] and phenylalanine [Phe]) that face the pore are thought to be high-affinity drug-binding sites. (B) Sequence comparisons between HERG and other potassium channels. With the exception of the closely related hEAG channel, the others have 1 or 2 prolines in S6 and 0 or 1 aromatic residues. As discussed in the text, these 2 features appear to determine the ease with which the HERG channel is blocked by a wide range of drugs. Adapted with permission from the Journal of Biological Chemistry (19).