Bithiazole correctors rescue CFTR mutants by two different mechanisms

Biochemistry. 2013 Aug 6;52(31):5161-3. doi: 10.1021/bi4008758. Epub 2013 Jul 22.

Abstract

Better correctors are needed to repair cystic fibrosis transmembrane conductance regulator (CFTR) processing mutants that cause cystic fibrosis. Determining where the correctors bind to CFTR would aid in the development of new correctors. A recent study reported that the second nucleotide-binding domain (NBD2) was involved in binding of bithiazole correctors. Here, we show that bithiazole correctors could also rescue CFTR mutants that lacked NBD2. These results suggest that bithiazoles rescue CFTR mutants by two different mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Mutation*
  • Protein Binding
  • Protein Structure, Tertiary
  • Thiazoles / chemistry
  • Thiazoles / metabolism*

Substances

  • Thiazoles
  • Cystic Fibrosis Transmembrane Conductance Regulator