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Structural and functional characterization of a protein isolated from Bothrops jararaca snake plasma, related to the mammalian high molecular weight kininogen

Grant number: 10/09002-8
Support type:Regular Research Grants
Duration: December 01, 2010 - November 30, 2012
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Luis Roberto de Camargo Gonçalves
Grantee:Luis Roberto de Camargo Gonçalves
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Fernanda Calheta Vieira Portaro ; Luiz Roberto Giorgetti de Britto ; Sandra Coccuzzo Sampaio Vessoni

Abstract

The Bothrops jararaca snake plasma is rich in protease inhibitors, some of which have inhibitory activity on toxins from its own venom. One of these, which have a molecular mass of 110 kDa, is a potent inhibitor of cysteine proteases and releases a peptide that induces contraction of homologous smooth musculature. For these characteristics this protein, named BjHK (Bothrops jararaca High Molecular Weight Kininogen) was correlated to mammalian high molecular weight kininogens. Moreover, it was found that this protein inhibits metalloproteases present in the B. jararaca venom. This effect was also observed in human high molecular weight kininogen and correlated to portions of the domain 5 of this protein. The aim of this project is search for homologies between BjHK and the human kininogen, by amino acid sequence and mass spectrometry. Furthermore, a possible inhibitory activity of this protein on platelet aggregation and cells adhesion will be tested; these activities were also described in human high molecular weight kininogen and correlated to their domain 5. Domain 5 of human kininogen is also described as an inhibitor of leukocyte migration and as this is the domain responsible for the inhibition of snake venom metalloproteinases, as mentioned above, it will be studied if the BjHK inhibits alterations in leukocyte-endothelial interactions induced by metalloproteases isolated from Bothrops jararaca venom. (AU)