Anticestodial effect of macrolactones related to FK506. Molecular characterization of FK-Binding Protein from Echinococcus granulosus.

CUMINO A. C.; LAMENZA P.; DENEGRI G. M.

Rosario, Argentina

Congreso; VIII Congreso Argentino de Protozoología y Enfermedades Parasitarias.; 2008

Sociedad Argentina Protozoología

The immunophilin superfamily consists of highly conserved, ubiquitously expressed proteins that possess rotamase (peptidyl prolyl cis-trans isomerase –PPIase-) activity and can play roles in protein folding and transport, RNA splicing and the regulation of multi-protein complexes in cells. These proteins binds to specific fungal natural drugs and can be classified in two families, cyclophilins (CyPs bind cyclosporine A) and FK506-binding proteins (FKBPs bind macrolides such as FK506 and rapamycin). Recently have seen a great increase in the number of known immunophilin genes in protozoa and helminths and unexpected roles in parasite virulence, host immnunomodulation and sexual differentiation have been suggested. In the present study, we concentrated on exploiting the use of rapamycin and derivated as an alternative and novel antiechinoccocal compound, firstly by carrying out a thorough molecular, structural and functional analysis of the drug receptor protein present in Echinococcus granulosus FKBP (EgFKBP).  The 15-kDa mature protein belongs at FKBP-C superfamily and it represents a homolog of FKBP from mammalian, sponges and insects. Furthermore, in view of the potent anticestodial activities of cyclosporins, macrolactones and derivates, we discussed the properties of EgFKBP in this parasite and the possible drug action in a block signal transduction processes dependent of calcium.