PAF receptor structure: a hypothesis.
Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong "Cache-orielles" (ear-muff) effect, i.e., two strong electronegative wells (isocontour at -10 Kcal/mole) are located at 180 degrees to each other and at a relatively constant distance. Initial consideration of the "Cache-oreilles" effect implied the structure of a bipolarized cylinder of 10-12 A diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.
Godfroid
J J
JJ
Laboratoire de Pharmacochimie Moléculaire, Université Paris 7, France.
Dive
G
G
Lamotte-Brasseur
J
J
Batt
J P
JP
Heymans
F
F
D008958:Models, Molecular; D008968:Molecular Conformation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor