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rBmTI-A is a recombinant serine protease inhibitor that belongs to the Kunitz-BPTI family and that was cloned from Rhipicephalus microplus tick. rBmTI-A has inhibitory activities on bovine trypsin, human plasma kallikrein, human neutrophil elastase and plasmin with dissociation constants in nM range. It is characterized by two inhibitory domains and each domain presents six cysteines that form three disulfide bonds, which contribute to the high stability of its structure. Previous studies suggest that serine protease inhibitor rBmTI-A has a protective potential against pulmonary emphysema in mice and anti-inflammatory potential, besides rBmTI-A presented a potent inhibitory activity against in vitro vessel formation. In this study, the tertiary structure of BmTI-A was modeled based on the structure of its Sabellastarte magnifica homologue. The structure stabilization was evaluated by molecular dynamics analysis. Circular dichroism data corroborated the secondary structure found by the homology modeling.Thermostability analysis confirmed the thermostability and the relation between the effects of the temperature in the inhibitor activity. The loss of activity observed was gradual, and, after 60 minutes of incubation at 90ºC the inhibitor lost it completely.

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28rBmTI-A is a recombinant serine protease inhibitor that belongs to the Kunitz-BPTI 29 family and that was cloned from Rhipicephalus microplus tick. rBmTI-A has inhibitory 30 activities on bovine trypsin, human plasma kallikrein, human neutrophil elastase and 31 plasmin with dissociation constants in nM range. It is characterized by two inhibitory 32 domains and each domain presents six cysteines that form three disulfide bonds, which 33 contribute to the high stability of its structure. Previous studies suggest that serine 34 protease inhibitor rBmTI-A has a protective potential against pulmonary emphysema in 35 mice and anti-inflammatory potential, besides rBmTI-A presented a potent inhibitory 36 activity against in vitro vessel formation. In this study, the tertiary structure of BmTI-A 37 was modeled based on the structure of its Sabellastarte magnifica homologue. The 38 structure stabilization was evaluated by molecular dynamics analysis. Circular 39 dichroism data corroborated the secondary structure found by the homology modeling. 40Thermostability analysis confirmed the thermostability and the relation between the 41 effects of the temperature in the inhibitor activity. The loss of activity observed was 42 gradual, and, after 60 minutes of incubation at 90ºC the inhibitor lost it completely. 43