New insights into the GABA(A) receptor structure and orthosteric ligand binding: receptor modeling guided by experimental data.

ABSTRACT: GABA(A) receptors (GABA(A)Rs) are ligand gated chloride ion channels that mediate overall inhibitory signaling in the CNS. A detailed understanding of their structure is important to gain insights in, e.g., ligand binding and functional properties of this pharmaceutically important target. Homology modeling is a necessary tool in this regard because experimentally determined structures are lacking. Here we present an exhaustive approach for creating a high quality model of the α(1)β(2)γ(2) subtype of the GABA(A)R ligand binding domain, and we demonstrate its usefulness in understanding details of orthosteric ligand binding. The model was constructed by using multiple templates and by incorporation of knowledge from biochemical/pharmacological experiments. It was validated on the basis of o

SUBMITTER: Sander T 

PROVIDER: S-EPMC3076690 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature