Toxins 2016, 8(7), 223; https://doi.org/10.3390/toxins8070223
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
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Institute of Biomedical Sciences, Laboratory of Immunoparasitology “Dr. Mario Endsfeldz Camargo”, Federal University of Uberlândia, Av. Pará 1720, Uberlândia 38400-902, Brazil
2
Institute of Biomedical Sciences, Laboratory of Biophysics, Federal University of Uberlândia, Av. Pará 1720, Uberlândia 38400-902, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen P. Mackessy
Received: 17 December 2015 / Revised: 4 July 2016 / Accepted: 7 July 2016 / Published: 20 July 2016
(This article belongs to the Special Issue Venomics, Venom Proteomics and Venom Transcriptomics)
Abstract
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. View Full-TextKeywords:
BmooMP-alpha-I; zinc metalloprotease; TNF; TACE
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MDPI and ACS Style
Silva, M.C.; Lopes Silva, T.; Silva, M.V.; Mota, C.M.; Santiago, F.M.; Fonseca, K.C.; Oliveira, F.; Mineo, T.W.P.; Mineo, J.R. 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. Toxins 2016, 8, 223.
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