Inhibitors of phospholipases A₂ in the blood plasma of snakes

FORTES-DIAS, C.L.(1)

FUNED, Belo Horizonte, MG

It has long been noted that several animal species are resistant to envenomation by snake bites. This natural immunity was ascribed, in most cases, to the presence in the blood of neutralizing factors active against distinct pharmacological venom activities. We have been focusing on phospholipase A₂ inhibitors present in the blood plasma of snakes, whose members have been organized into three different classes (alpha, beta and gamma) according to their structural features and specificities (1). A gamma- inhibitor (CNF) from the blood plasma of South American rattlesnake Crotalus durissusterrificus has been taken as our model. CNF was cloned and sequenced from the encoding cDNA (2) and is composed of two structural units known as three finger motifs, similar to those found in the urokinase-type plasminogen activator receptor (u-PAR) and Ly-6 related proteins (1). CNF is a hexameric glycoprotein of 160 kDa that acts by replacing the PLA₂ subunit (CB) in the heterodimericcrotoxin(CACB), thereby neutralizing its toxicity (2,3). Protein-protein interactions in CACB and CACNF complexes have been studied through binding experiments to synaptosomes and SPOT technology (4).

REFERENCES

1)Ohkura, N, Okuhara, H, Inoue, S, Ikeda, K & Hayashi, K (1997). Biochem. J. 325: 527-531.

2)Fortes-Dias, CL, Lin, Y, Ewell, J, Diniz, CR. & Liu, T-Y (1994) J. Biol. Chem. 269: 15646-15651.

3)Perales, J, Villela, C, Domont, GB, Choumet, V, Saliou, B, Moussatché, H, Bon, C & Faure, G (1995) Eur. J. Biochem. 227: 19-26.

4)Molina, F., Laune, D, Gougat, C, Pau, B & Granier, C (1996) Peptide Res. 9: 151-153.

CORRESPONDENCE TO:

FORTES-DIAS, C.L., R. José Mendes de Carvalho 250, Belo Horizonte, MG, CEP: 30840-350, Brasil, E.mail: consuelo@funed.mg.gov.br