Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism.

ABSTRACT: Small molecules that correct protein misfolding and misprocessing defects offer a potential therapy for numerous human diseases. However, mechanisms underlying pharmacological correction of such defects, especially in heteromeric complexes with structurally diverse constituent proteins, are not well understood. Here we investigate how two chemically distinct compounds, glibenclamide and carbamazepine, correct biogenesis defects in ATP-sensitive potassium (KATP) channels composed of sulfonylurea receptor 1 (SUR1) and Kir6.2. We present evidence that despite structural differences, carbamazepine and glibenclamide compete for binding to KATP channels, and both drugs share a binding pocket in SUR1 to exert their effects. Moreover, both compounds engage Kir6.2, in particular the distal N termin

SUBMITTER: Devaraneni PK 

PROVIDER: S-EPMC4367296 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature