Unnatural amino acid mutagenesis of the GABA(A) receptor binding site residues reveals a novel cation-pi interaction between GABA and beta 2Tyr97.

ABSTRACT: The binding pockets of Cys-loop receptors are dominated by aromatic amino acids. In the GABA(A) receptor alpha1Phe65, beta2Tyr97, beta2Tyr157, and beta2Tyr205 are present at the beta2/alpha1 interface and have been implicated in forming an important part of the GABA binding site. Here, we have probed interactions of these residues using subtle chemical changes: unnatural amino acid mutagenesis was used to introduce a range of Phe analogs, and mutant receptors expressed in oocytes were studied using voltage-clamp electrophysiology. Serial mutations at beta(2)97 revealed a approximately 20-fold increase in EC50 with the addition of each fluorine atom to a phenylalanine, indicating a cation-pi interaction between GABA and this residue. This is the first example of a cation-pi interaction in l

SUBMITTER: Padgett CL 

PROVIDER: S-EPMC2649369 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature