Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors

FEBS Lett. 2007 Oct 2;581(24):4718-22. doi: 10.1016/j.febslet.2007.08.068. Epub 2007 Sep 6.

Abstract

Benzodiazepines are widely used drugs exerting sedative, anxiolytic, muscle relaxant, and anticonvulsant effects by acting through specific high affinity binding sites on some GABA(A) receptors. It is important to understand how these ligands are positioned in this binding site. We are especially interested here in the conformation of loop A of the alpha(1)beta(2)gamma(2) GABA(A) receptor containing a key residue for the interaction of benzodiazepines: alpha(1)H101. We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Asparagine / genetics
  • Asparagine / metabolism
  • Benzodiazepines / chemistry
  • Benzodiazepines / pharmacology*
  • Binding Sites
  • Cell Line
  • Humans
  • Ligands
  • Molecular Structure
  • Mutation / genetics
  • Phenylalanine / genetics
  • Phenylalanine / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*

Substances

  • Ligands
  • Protein Subunits
  • Receptors, GABA-A
  • Benzodiazepines
  • Phenylalanine
  • Asparagine