THE 3D HOMOLOGY MODEL OF THE FIRST NEUROTOXIC PEPTIDE (TF4) FROM THE SCORPION Tityus fasciolatus

Barbosa, J.A.R.G.(1), Wagner, S.(2),  Castro, M.S.(2,3), Fontes, W.(3), Sousa, M.V.(3), Schwartz, E.F.(2), Pires Jr., O.R.(2), Sebben, A.(2), Schwartz, C.A.(2)

(1)Centro de Biologia Molecular Estrutural - Laboratório Nacional de Luz Síncrotron  (CeBiMe-LNLS), Campinas, SP, Brasil, (2)Laboratório de Toxinologia, CFS, IB, Universidade de Brasília, Brasília, DF, Brasil, (3)Centro Brasileiro de Serviços e Pesquisas em Proteínas, Universidade de Brasília, Brasília, DF, Brasil.

The scorpion Tityus fasciolatus is endemic to the central region of Brazil, where human envenomation has been reported. One neurotoxic peptide, named Tf4, was purified from this venom and sequenced. Tf4 has 6.6 kDa and delays frog sodium channel inactivation reversibly. The complete sequencing of Tf4 allowed us to search the protein data bank (PDB) for similar sequences of proteins that had their 3D structure known. There were 18 hits in total and identities of the 18 sequences with the Tf4 sequence were between 31 and 67%. Four structures were used to build the 3D homology model of Tf4: Ts1, PDB code 1B7D; Cse-v5, PDB code 1I6F; Cse-v3, PDB code 2SN3 and BmK-M8, PDB code 1SNB. The program O was used to superimpose the Ts1, Cse-v5, Cse-v3 and BmK-M8 structures and build the Tf4 model. Most of the model followed the Ts1 structure that has the highest identity with Tf4. No insertions or deletions are found between Tf4 and Ts1, except for the additional glycine N-terminal residue in Tf4. This longer N-terminus and the other 20 residues that are different between the two sequences contribute to the weaker toxic activity presented by Tf4 when compared to Ts1. A study based on the Tf4 model showing possible candidates for this loss of activity, focusing on the differences shared with Ts1, will be presented.

CORRESPONDENCE TO:

W. Fontes, Centro Brasileiro de Serviços e Pesquisas em Proteínas, Universidade de Brasília, 70910-900, Brasília, DF, Brasil, Email: wagnerf@unb.br