Produção Nacional
Revisado por pares
Molecular cloning, functional expression, and molecular modeling of bothrostatin, a new highly active disintegrin from Bothrops jararaca venom
2005; Elsevier BV; Volume: 329; Issue: 2 Linguagem: Inglês
10.1016/j.bbrc.2005.01.148
ISSN1090-2104
AutoresJorge Hernández Fernández, Carlos Alberto-Silva, Marina T. Assakura, Antônio Carlos Martins de Camargo, Solange M.T. Serrano,
Tópico(s)Biochemical and Structural Characterization
ResumoDisintegrins are among the most potent antagonists of several integrins. A cDNA encoding a novel disintegrin, bothrostatin, was cloned from a Bothrops jararaca cDNA library. The precursor of bothrostatin contains a pro, a metalloproteinase, and an RGD-disintegrin domain. The disintegrin domain expressed in Escherichia coli showed high inhibitory activity on collagen-induced platelet aggregation (IC50 of 12 nM), and thus it can be used as a useful tool for studies of integrin–ligand interaction. Furthermore, we used the comparative modeling approach to obtain a model of the 3D structure of bothrostatin. Our results suggest that bothrostatin adopts a globular, closed structure in solution. The RGD motif is exposed to the solution by the loop formed by residues 45–59 and is very close to the C-terminal domain forming a finger-like structure. The proximity of the RGD loop and the C-terminal residues, which is maintained by the Cys47–Cys66 bond, suggests that the C-terminal residues are involved in the ability of bothrostatin to interact with its ligands.
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