Purpose: The aim of this work is to identify structural features regarding the biochemical and biological activities of LOPAP (Lonomia obliqua prothrombin activator protease), a lipocalin that is related to the coagulant syndrome triggered during the envenoming by this specie.

Materials and Methods: Homology modeling using Modeller 8v2 was the chosen method to predict LOPAP's structural features. For the monomeric form, the structures of Insecticyanin (PDB: 1Z24) and engineered Bilin Binding Protein variants (PDB: 1KXO and 1N0S) were taken as templates. For the tetrameric form modeling, the structure of Bilin Binding Protein (PDB: 1BBP) was chosen. From 20 initial models of each form (monomeric and tetrameric), it was taken that with the best variable target function score for subsequent steps. Then, the model was checked for the presence of serinoprotease catalytic residues using Catalytic Site Atlas (CSA). The residues indicated by CSA were refined by rotamer searching and the whole model was submitted to energy minimization using GROMOS96 implemented in Swiss PDB Viewer. Since "in vitro" observations indicated that the catalytic activity of LOPAP is positively affected by the presence of calcium, the GG software was employed for calcium binding site prediction.

Results: The Lopap monomer model shows the characteristic lipocalins basket-like b-barrel formed by eight b-strands and a conserved a-helix. The search for serinoprotease active residues using CSA, predicted that the residues His168, Glu171 and a Ser119 could be related to the serinoprotease-like activity of LOPAP. The, GG software found two putative calcium binding sites. One of then is probably related to the stabilization of the putative active site. The tetrameric LOPAP model suggests that the each subunit interact with a second subunit by its C-terminal portion and with a third subunit by b-strand 1 and the loops between three pairs of b-strands. In each subunit, the active site and the hydrophobic pocket entrance remains accessible for the solvent.

Conclusions: These results indicate structural features in the predicted models that could justify LOPAP's serinoprotease-like activity and the influence of calcium as an activity enhancer. SUPPORT: FAPESP / CNPq