Lysophospholipid interactions with protein targets.
Bioactive lysophospholipids include lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), cyclic-phosphatidic acid (CPA) and alkyl glycerolphosphate (AGP). These lipid mediators stimulate a variety of responses that include cell survival, proliferation, migration, invasion, wound healing, and angiogenesis. Responses to lysophospholipids depend upon interactions with biomolecular targets in the G protein-coupled receptor (GPCR) and nuclear receptor families, as well as enzymes. Our current understanding of lysophospholipid interactions with these targets is based on a combination of lysophospholipid analog structure activity relationship studies as well as more direct structural characterization techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and experimentally-validated molecular modeling. The direct structural characterization studies are the focus of this review, and provide the insight necessary to stimulate structure-based therapeutic lead discovery efforts in the future.
Parrill
Abby L
AL
Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA. aparrill@memphis.edu
D000818:Animals; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D049312:Receptors, Lysophospholipid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D008246:Lysophospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D049312:Receptors, Lysophospholipid