title: Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate.
abstract: Originating from its DNA sequence, a computational model of the Edg1 receptor has been developed that predicts critical interactions with its ligand, sphingosine 1-phosphate. The basic amino acids Arg(120) and Arg(292) ion pair with the phosphate, whereas the acidic Glu(121) residue ion pairs with the ammonium moiety of sphingosine 1-phosphate. The requirement of these interactions for specific ligand recognition has been confirmed through examination of site-directed mutants by radioligand binding, ligand-induced [(35)S]GTPgammaS binding, and receptor internalization assays. These ion-pairing interactions explain the ligand specificity of the Edg1 receptor and provide insight into ligand specificity differences within the Edg receptor family. This computational map of the ligand binding pocket provides information necessary for understanding the molecular pharmacology of this receptor, thus underlining the potential of the computational method in predicting ligand-receptor interactions.
authors.affiliation: Department of Chemistry and Computational Research on Materials Institute, University of Memphis, Memphis, Tennessee 38152-6060, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Parrill
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: D L
authors.initials: DL
authors.lastname: Bautista
authors.forename: J R
authors.initials: JR
authors.lastname: Van Brocklyn
authors.forename: Z
authors.initials: Z
authors.lastname: Lorincz
authors.forename: D J
authors.initials: DJ
authors.lastname: Fischer
authors.forename: D L
authors.initials: DL
authors.lastname: Baker
authors.forename: K
authors.initials: K
authors.lastname: Liliom
authors.forename: S
authors.initials: S
authors.lastname: Spiegel
authors.forename: G
authors.initials: G
authors.lastname: Tigyi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D003198:Computer Simulation; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007477:Ions; D008024:Ligands; D008246:Lysophospholipids; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D017386:Sequence Homology, Amino Acid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D017874:Immediate-Early Proteins; D007477:Ions; D008024:Ligands; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D018698:Glutamic Acid; D001120:Arginine; D013110:Sphingosine