title: Structure of the first sphingosine 1-phosphate receptor.
abstract: The sphingosine 1-phosphate receptor 1 (S1P₁) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P₁ is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors has now enabled the elucidation of the structure of S1P₁. Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P₁ crystal structure will be helpful for designing ligands that specifically target S1P₁.
authors.affiliation: Department of Chemistry, The University of Memphis, 213 Smith Chemistry Building, Memphis, TN 38152, USA. aparrill@memphis.edu
authors.forename: Abby L
authors.initials: AL
authors.lastname: Parrill
authors.forename: Santiago
authors.initials: S
authors.lastname: Lima
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: D000813:Anilides / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007189:Indans / Q000378:metabolism / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism; D008958:Models, Molecular; D063065:Organophosphonates / Q000378:metabolism / Q000494:pharmacology; D010069:Oxadiazoles / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C532995:2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl amino)ethanol; C513113:3-amino-4-(3-hexylphenylamino)-4-oxobutylphosphonic acid; D000813:Anilides; D007189:Indans; D008246:Lysophospholipids; D063065:Organophosphonates; D010069:Oxadiazoles; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine