Binding Site Of Suramin In K49 PLA2s. 

¹Murakami, M.T.; ¹Gava, L.M.; ²Melo, P.A.; ³Gutiérrez, J.M.; ²Arruda, E.Z. ¹Arni, R.K.

1 Departamento de Física – IBILCE/UNESP – São José do Rio Preto, São Paulo, Brazil. 2 Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro. 3 Instituto Clodomiro Picado, Facultad de Microbiologia, Universidad de Costa Rica, San Jose, Costa Rica.

Suramin is a polysulfonated naphthylurea derivative (molecular mass 1429), which is used as a primary agent in the treatment of African trypanosomiasis (African sleeping sickness; Trypanosome fever) caused by Trypanosomabrucei gambiense or T. b. rhodesiense. Besides, suramin is used as a secondary agent in the treatment of onchocericiasis (river blindness) caused by Onchocercavolvulus. Recent studies reveals that suramin inhibits the myotoxicity of snake venoms via especific interactions with basic K49 PLA2s, which play a major role in the myotoxicity of the snake venoms.

We have crystallized and solved the crystal structure of suramin complexed with a basic K49 PLA2 from Bothropsasper venom. The structural analysis demonstrated that the polysulfonated region of suramin binds the residues R34, K53 and K69, that results in a significant modification in the surface eletrostatical potential of the protein. The negative profile acquired by K49 PLA2 due the presence of suramin might be responsible for the loss of myotoxic activity. Another hyphotesis is that the close presence of suramin (intermediate region) in the catalytic site may result in steric impediment for myotoxicity. Thus suramin can be used concomitantly with other drugs for the treatment of snake envenomation and could serve as an important tool to understand the poorly know mechanism involved in myotoxicity. This work reports the first crystallographic structure of  a complex suramin-protein.

Support: FAPESP, CNPq and CAPES.

Correspondence to: qualitus@uol.com.br