ArticleProtein science : a publication of the Protein Society2003
Construction of a sequence motif characteristic of aminergic G protein-coupled receptors.
Article in Protein science : a publication of the Protein Society, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed.
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- Enigmatic Histamine Receptor HLife (Basel, Switzerland) · 2020Review
- Phenylethylamides derived from bacterial secondary metabolites specifically inhibit an insect serotonin receptor.Scientific reports · 2019Article
- Spermine in semen of male sea lamprey acts as a sex pheromone.PLoS biology · 2019Article
- A Complete Assessment of Dopamine Receptor- Ligand Interactions through Computational Methods.Molecules (Basel, Switzerland) · 2019Article
- The Trace Amine-Associated Receptor 1 Agonist 3-Iodothyronamine Induces Biased Signaling at the Serotonin 1b Receptor.Frontiers in pharmacology · 2018Article
- Elimination of a ligand gating site generates a supersensitive olfactory receptor.Scientific reports · 2016Article
- High-affinity olfactory receptor for the death-associated odor cadaverine.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Identification of novel arthropod vector G protein-coupled receptors.Parasites & vectors · 2013Article
- Article
- Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.PloS one · 2011Article
- Interactions of the melanocortin-4 receptor with the peptide agonist NDP-MSH.Journal of molecular biology · 2010Article
- Probing the role of the cation-pi interaction in the binding sites of GPCRs using unnatural amino acids.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Trace amine-associated receptor 1-Family archetype or iconoclast?Pharmacology & therapeutics · 2007Review
- The pK(a) Distribution of Drugs: Application to Drug Discovery.Perspectives in medicinal chemistry · 2007Article
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Abstract
An approach to discover sequence patterns characteristic of ligand classes is described and applied to aminergic G protein-coupled receptors (GPCRs). Putative ligand-binding residue positions were inferred from considering three lines of evidence: conservation in the subfamily absent or underrepresented in the superfamily, any available mutation data, and the physicochemical properties of the ligand. For aminergic GPCRs, the motif is composed of a conserved aspartic acid in the third transmembrane (TM) domain (rhodopsin position 117) and a conserved tryptophan in the seventh TM domain (rhodopsin position 293); the roles of each are readily justified by molecular modeling of ligand-receptor interactions. This minimally defined motif is an appropriate computational tool for identifying additional, potentially novel aminergic GPCRs from a set of experimentally uncharacterized "orphan" GPCRs, complementing existing sequence matching, clustering, and machine-learning techniques. Motif sensitivity stems from the stepwise addition of residues characteristic of an entire class of ligand (and not tailored for any particular biogenic amine). This sensitivity is balanced by careful consideration of residues (evidence drawn from mutation data, correlation of ligand properties to residue properties, and location with respect to the extracellular face), thereby maintaining specificity for the aminergic class. A number of orphan GPCRs assigned to the aminergic class by this motif were later discovered to be a novel subfamily of trace amine GPCRs, as well as the successful classification of the histamine H4 receptor.
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