Pharmacophore model for bile acids recognition by the FPR receptor.
Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation through the molecular recognition of chemotactic factors. A large number of structurally diverse chemotypes modulate the activity of FPRs. Newly identified antagonists include bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The molecular recognition of these compounds at FPR receptor was computationally investigated using both ligand- and structure-based approaches. Our findings suggest that all antagonists bind at the first third of the seven helical bundles. A closer inspection of bile acid interaction reveals a number of unexploited anchor points in the binding site that may be used to aid the design of new potent and selective bile acids derivatives at FPR.
Ferrari
Cristina
C
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, via del Liceo 1, 06127 Perugia, Italy.
Macchiarulo
Antonio
A
Costantino
Gabriele
G
Pellicciari
Roberto
R
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001665:Binding Sites; D002417:Cattle; D008958:Models, Molecular; D010455:Peptides / Q000037:antagonists & inhibitors; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001647:Bile Acids and Salts; D010455:Peptides; D044042:Receptors, Formyl Peptide