Probing the outer mouth structure of the HERG channel with peptide toxin footprinting and molecular modeling.

ABSTRACT: Previous studies have shown that the unusually long S5-P linker lining human ether a-go-go related gene's (hERG's) outer vestibule is critical for its channel function: point mutations at high-impact positions here can interfere with the inactivation process and, in many cases, also reduce the pore's K+ selectivity. Because no data are available on the equivalent region in the available K channel crystal structures to allow for homology modeling, we used alternative approaches to model its three-dimensional structure. The first part of this article describes mutant cycle analysis used to identify residues on hERG's outer vestibule that interact with specific residues on the interaction surface of BeKm-1, a peptide toxin with known NMR structure and a high binding affinity to hERG. The seco

SUBMITTER: Tseng GN 

PROVIDER: S-EPMC1853143 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature