Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance

• Published in: Toxins 2016-07, Vol.8 (7), p.223
• Main Authors: Silva, Maraisa Cristina, Lopes Silva, Tamires, Silva, Murilo Vieira, Mota, Caroline Martins, Santiago, Fernanda Maria, Fonseca, Kelly Cortes, Oliveira, Fábio, Mineo, Tiago Wilson Patriarca, Mineo, José Roberto
• Format: Article
• Language: English
• Subjects: Animals; BmooMP-alpha-I; Bothrops; Cells, Cultured; Crotalid Venoms - chemistry; Crotalid Venoms - metabolism; Crotalid Venoms - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Male; Metalloendopeptidases - chemistry; Metalloendopeptidases - metabolism; Metalloendopeptidases - pharmacology; Mice, Inbred C57BL; Molecular Docking Simulation; Protein Binding; Protein Conformation; Proteolysis; Reptilian Proteins - chemistry; Reptilian Proteins - metabolism; Reptilian Proteins - pharmacology; Structure-Activity Relationship; Substrate Specificity; TACE; TNF; Toll-Like Receptors - agonists; Toll-Like Receptors - metabolism; Tumor Necrosis Factor-alpha - chemistry; Tumor Necrosis Factor-alpha - metabolism; Zinc - chemistry; Zinc - metabolism; zinc metalloprotease
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins8070223

Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation.