title: A chemogenomic analysis of the transmembrane binding cavity of human G-protein-coupled receptors.
abstract: The amino acid sequences of 369 human nonolfactory G-protein-coupled receptors (GPCRs) have been aligned at the seven transmembrane domain (TM) and used to extract the nature of 30 critical residues supposed--from the X-ray structure of bovine rhodopsin bound to retinal--to line the TM binding cavity of ground-state receptors. Interestingly, the clustering of human GPCRs from these 30 residues mirrors the recently described phylogenetic tree of full-sequence human GPCRs (Fredriksson et al., Mol Pharmacol 2003;63:1256-1272) with few exceptions. A TM cavity could be found for all investigated GPCRs with physicochemical properties matching that of their cognate ligands. The current approach allows a very fast comparison of most human GPCRs from the focused perspective of the predicted TM cavity and permits to easily detect key residues that drive ligand selectivity or promiscuity.
authors.affiliation: Bioinformatics of the Drug, CNRS UMR7081, Illkirch, France.
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Surgand
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodrigo
authors.forename: Esther
authors.initials: E
authors.lastname: Kellenberger
authors.forename: Didier
authors.initials: D
authors.lastname: Rognan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D023281:Genomics; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000145:classification / Q000235:genetics*
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled