Distinct agonist- and antagonist-binding sites on the glycine receptor.
The distinction between receptor-binding sites for agonists and antagonists underpins the pharmacological differences between these two classes of ligands. In the glycine receptor, antagonist (strychnine) binding requires an interaction with residues Lys-200 and Tyr-202. We now demonstrate that the agonist-binding site of this receptor is located at the residue Thr-204. The agonist-binding site interaction is thus likely to be mediated by hydrogen bonding and not by ionic interactions. Our results demonstrate that, in contrast to other studies of ligand-gated ion channel receptors, agonist- and antagonist-binding sites are composed of distinct amino acid residues.
Vandenberg
R J
RJ
Garvan Institute of Medical Research, Darlinghurst NSW, Australia.
Handford
C A
CA
Schofield
P R
PR
D000409:Alanine / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013331:Strychnine / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*
D008024:Ligands; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D013654:Taurine; D013331:Strychnine; D000409:Alanine; D005998:Glycine