Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis.

ABSTRACT:

Background and purpose

β2/3-subunit-selective modulation of GABAA receptors by valerenic acid (VA) is determined by the presence of transmembrane residue β2/3N265. Currently, it is not known whether β2/3N265 is part of VA's binding pocket or is involved in the transduction pathway of VA's action. The aim of this study was to clarify the localization of VA's binding pocket on GABAA receptors.

Experimental approach

Docking and a structure-based three-dimensional pharmacophore were employed to identify candidate amino acid residues that are likely to interact with VA. Selected amino acid residues were mutated, and VA-induced modulation of the resulting GABAA receptors expressed in Xenopus oocytes was analysed.

Key results

A binding pocket for VA at the β(+) /α(-) interfa

SUBMITTER: Luger D 

PROVIDER: S-EPMC4988470 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature