Sphingosine 1-phosphate and lysophosphatidic acid receptors: agonist and antagonist binding and progress toward development of receptor-specific ligands.
Sphingosine 1-phosphate and lysophosphatidic acid are two phospholipid growth factors whose importance in physiology and pathophysiology is becoming more and more apparent. Structure-activity relationships for agonism and antagonism at the thirteen known cell-surface and one intracellular receptor are described. Particular emphasis is placed on ligands having different selectivity than the parent molecules. Structural insights regarding agonist and antagonist recognition by the receptors from both computational modeling studies and crystallography are also discussed.
Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152, USA. aparrill@memphis.edu
Abby L
AL
Parrill
Vineet M
VM
Sardar
Hongbin
H
Yuan
D000818:Animals; D006801:Humans; D008024:Ligands; D047495:PPAR gamma / Q000378:metabolism; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors*; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D008024:Ligands; D047495:PPAR gamma; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid