Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate

Abby L. Parrill, De An Wang, Debra L. Bautista, James R. Van Brocklyn, Zsolt Lorincz, David J. Fischer, Daniel L. Baker, Karoly Liliom, Sarah Spiegel, Gabor Tigyi

Research output: Contribution to journalArticle

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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 Arg120 and Arg292 ion pair with the phosphate, whereas the acidic Glu121 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 [35S]GTPγS 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.

Original languageEnglish (US)
Pages (from-to)39379-39384
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number50
DOIs
StatePublished - Dec 15 2000

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Ligands
Ions
Lysosphingolipid Receptors
Basic Amino Acids
DNA sequences
Computational methods
sphingosine 1-phosphate
Ammonium Compounds
Assays
Phosphates
Pharmacology

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Parrill, A. L., Wang, D. A., Bautista, D. L., Van Brocklyn, J. R., Lorincz, Z., Fischer, D. J., ... Tigyi, G. (2000). Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate. Journal of Biological Chemistry, 275(50), 39379-39384. https://doi.org/10.1074/jbc.M007680200

Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate. / Parrill, Abby L.; Wang, De An; Bautista, Debra L.; Van Brocklyn, James R.; Lorincz, Zsolt; Fischer, David J.; Baker, Daniel L.; Liliom, Karoly; Spiegel, Sarah; Tigyi, Gabor.

In: Journal of Biological Chemistry, Vol. 275, No. 50, 15.12.2000, p. 39379-39384.

Research output: Contribution to journalArticle

Parrill, AL, Wang, DA, Bautista, DL, Van Brocklyn, JR, Lorincz, Z, Fischer, DJ, Baker, DL, Liliom, K, Spiegel, S & Tigyi, G 2000, 'Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate', Journal of Biological Chemistry, vol. 275, no. 50, pp. 39379-39384. https://doi.org/10.1074/jbc.M007680200
Parrill AL, Wang DA, Bautista DL, Van Brocklyn JR, Lorincz Z, Fischer DJ et al. Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate. Journal of Biological Chemistry. 2000 Dec 15;275(50):39379-39384. https://doi.org/10.1074/jbc.M007680200
Parrill, Abby L. ; Wang, De An ; Bautista, Debra L. ; Van Brocklyn, James R. ; Lorincz, Zsolt ; Fischer, David J. ; Baker, Daniel L. ; Liliom, Karoly ; Spiegel, Sarah ; Tigyi, Gabor. / Identification of Edg1 receptor residues that recognize sphingosine 1-Phosphate. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 50. pp. 39379-39384.
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