Multiple Tyrosine Residues Contribute to GABA Binding in the GABA(C) Receptor Binding Pocket.

ABSTRACT: The ligand binding site of Cys-loop receptors is dominated by aromatic amino acids. In GABA(C) receptors, these are predominantly tyrosine residues, with a number of other aromatic residues located in or close to the binding pocket. Here we examine the roles of these residues using substitution with both natural and unnatural amino acids followed by functional characterization. Tyr198 (loop B) has previously been shown to form a cation-π interaction with GABA; the current data indicate that none of the other aromatic residues form such an interaction, although the data indicate that both Tyr102 and Phe138 may contribute to stabilization of the positively charged amine of GABA. Tyr247 (loop C) was very sensitive to substitution and, combined with data from a model of the receptor, suggest a

SUBMITTER: Lummis SC 

PROVIDER: S-EPMC3309607 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature