title: 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.
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.
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. maraisacris@doutorado.ufu.br.
authors.forename: Maraisa Cristina
authors.initials: MC
authors.lastname: Silva
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. tlopes_s@yahoo.com.br.
authors.forename: Tamires
authors.initials: T
authors.lastname: Lopes Silva
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. murilo.vieira@ufu.br.
authors.forename: Murilo Vieira
authors.initials: MV
authors.lastname: Silva
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. carolinemartinsm@doutorado.ufu.br.
authors.forename: Caroline Martins
authors.initials: CM
authors.lastname: Mota
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. nandasantiago@hotmail.com.
authors.forename: Fernanda Maria
authors.initials: FM
authors.lastname: Santiago
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Biophysics, Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. kellyfonseca2003@yahoo.com.br.
authors.forename: Kelly Cortes
authors.initials: KC
authors.lastname: Fonseca
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Biophysics, Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. foliveira@umuarama.ufu.br.
authors.forename: Fábio
authors.initials: F
authors.lastname: Oliveira
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. tiago.mineo@ufu.br.
authors.forename: Tiago Wilson Patriarca
authors.initials: TW
authors.lastname: Mineo
authors.affiliation: Institute of Biomedical Sciences, Laboratory of Immunoparasitology "Dr. Mario Endsfeldz Camargo", Federal University of Uberl&#226;ndia, Av. Par&#225; 1720, Uberl&#226;ndia 38400-902, Brazil. jrmineo@ufu.br.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Mineo
mesh_terms: D000818:Animals; D017837:Bothrops; D002478:Cells, Cultured; D003435:Crotalid Venoms / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D059748:Proteolysis; D030162:Reptilian Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003435:Crotalid Venoms; D030162:Reptilian Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C000624528:BmooMP-alpha-I, Bothrops moojeni; D008666:Metalloendopeptidases; D015032:Zinc
keywords: BmooMP-alpha-I; TACE; TNF; zinc metalloprotease