Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists.
Pless SA
,
Hanek AP
,
Price KL
,
Lynch JW
,
Lester HA
,
Dougherty DA
,
Lummis SC
.
???displayArticle.abstract???
Cation-π interactions have been demonstrated to play a major role in agonist-binding in Cys-loop receptors. However, neither the aromatic amino acid contributing to this interaction nor its location is conserved among Cys-loop receptors. Likewise, it is not clear how many different agonists of a given receptor form a cation-π interaction or, if they do, whether it is with the same aromatic amino acid as the major physiological agonist. We demonstrated previously that Phe159 in the glycine receptor (GlyR) α1 subunit forms a strong cation-π interaction with the principal agonist, glycine. In the current study, we investigated whether the lower efficacy agonists of the human GlyR β-alanine and taurine also form cation-π interactions with Phe159. By incorporating a series of unnatural amino acids, we found cation-π interactions between Phe159 and the amino groups of β-alanine and taurine. The strengths of these interactions were significantly weaker than for glycine. Modeling studies suggest that β-alanine and taurine are orientated subtly differently in the binding pocket, with their amino groups further from Phe159 than that of glycine. These data therefore show that similar agonists can have similar but not identical orientations and interactions in the binding pocket and provide a possible explanation for the lower potencies of β-alanine and taurine.
Beene,
Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine.
2002, Pubmed,
Xenbase
Beene,
Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine.
2002,
Pubmed
,
Xenbase
Beene,
Tyrosine residues that control binding and gating in the 5-hydroxytryptamine3 receptor revealed by unnatural amino acid mutagenesis.
2004,
Pubmed
,
Xenbase
Beene,
Unnatural amino acid mutagenesis in mapping ion channel function.
2003,
Pubmed
,
Xenbase
Bocquet,
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.
2009,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Colquhoun,
A note on correlations in single ion channel records.
1987,
Pubmed
De Saint Jan,
Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA.
2001,
Pubmed
,
Xenbase
Dougherty,
Cys-loop neuroreceptors: structure to the rescue?
2008,
Pubmed
Dougherty,
Unnatural amino acids as probes of protein structure and function.
2000,
Pubmed
Farroni,
Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors.
2004,
Pubmed
Furchgott,
Metabolic factors that influence contractility of vascular smooth muscle.
1966,
Pubmed
Gallivan,
Cation-pi interactions in structural biology.
1999,
Pubmed
Grudzinska,
The beta subunit determines the ligand binding properties of synaptic glycine receptors.
2005,
Pubmed
Harvey,
GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization.
2004,
Pubmed
Hibbs,
Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.
2009,
Pubmed
Hilf,
Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.
2009,
Pubmed
Hilf,
X-ray structure of a prokaryotic pentameric ligand-gated ion channel.
2008,
Pubmed
Kearney,
Dose-response relations for unnatural amino acids at the agonist binding site of the nicotinic acetylcholine receptor: tests with novel side chains and with several agonists.
1996,
Pubmed
,
Xenbase
Killcross,
Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala.
1997,
Pubmed
Lape,
On the nature of partial agonism in the nicotinic receptor superfamily.
2008,
Pubmed
Laube,
Modulation of glycine receptor function: a novel approach for therapeutic intervention at inhibitory synapses?
2002,
Pubmed
Legendre,
The glycinergic inhibitory synapse.
2001,
Pubmed
Le Novère,
The Ligand Gated Ion Channel database: an example of a sequence database in neuroscience.
2001,
Pubmed
Lewis,
Kinetic determinants of agonist action at the recombinant human glycine receptor.
2003,
Pubmed
Lummis,
A cation-pi binding interaction with a tyrosine in the binding site of the GABAC receptor.
2005,
Pubmed
Lynch,
Molecular structure and function of the glycine receptor chloride channel.
2004,
Pubmed
Mecozzi,
Cation-pi interactions in aromatics of biological and medicinal interest: electrostatic potential surfaces as a useful qualitative guide.
1996,
Pubmed
Miyazawa,
Structure and gating mechanism of the acetylcholine receptor pore.
2003,
Pubmed
Mu,
Different binding orientations for the same agonist at homologous receptors: a lock and key or a simple wedge?
2003,
Pubmed
Nowak,
In vivo incorporation of unnatural amino acids into ion channels in Xenopus oocyte expression system.
1998,
Pubmed
,
Xenbase
Padgett,
Unnatural amino acid mutagenesis of the GABA(A) receptor binding site residues reveals a novel cation-pi interaction between GABA and beta 2Tyr97.
2007,
Pubmed
,
Xenbase
Pless,
Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy.
2009,
Pubmed
Pless,
Conformational variability of the glycine receptor M2 domain in response to activation by different agonists.
2007,
Pubmed
,
Xenbase
Pless,
A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue.
2008,
Pubmed
,
Xenbase
Rajendra,
Mutation of an arginine residue in the human glycine receptor transforms beta-alanine and taurine from agonists into competitive antagonists.
1995,
Pubmed
Rajendra,
The unique extracellular disulfide loop of the glycine receptor is a principal ligand binding element.
1995,
Pubmed
Reeves,
Prediction of 5-HT3 receptor agonist-binding residues using homology modeling.
2003,
Pubmed
Schmieden,
Pharmacology of the inhibitory glycine receptor: agonist and antagonist actions of amino acids and piperidine carboxylic acid compounds.
1995,
Pubmed
,
Xenbase
Schmieden,
Mutation of glycine receptor subunit creates beta-alanine receptor responsive to GABA.
1993,
Pubmed
,
Xenbase
Schmieden,
Agonist pharmacology of neonatal and adult glycine receptor alpha subunits: identification of amino acid residues involved in taurine activation.
1992,
Pubmed
,
Xenbase
Thompson,
The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5-HT3 receptors.
2007,
Pubmed
,
Xenbase
Thompson,
Locating an antagonist in the 5-HT3 receptor binding site using modeling and radioligand binding.
2005,
Pubmed
Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed
Vafa,
Identification of a new ligand binding domain in the alpha1 subunit of the inhibitory glycine receptor.
1999,
Pubmed
Vandenberg,
Distinct agonist- and antagonist-binding sites on the glycine receptor.
1992,
Pubmed
Xiu,
Nicotine binding to brain receptors requires a strong cation-pi interaction.
2009,
Pubmed
,
Xenbase
Yang,
Tropisetron modulation of the glycine receptor: femtomolar potentiation and a molecular determinant of inhibition.
2007,
Pubmed
Zhong,
From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding site in the nicotinic receptor.
1998,
Pubmed
