A structurally unique Fusobacterium nucleatumtannase provides detoxicant activity againstgallotannins and pathogen resistance

A structurally unique Fusobacterium nucleatumtannase provides detoxicant activity againstgallotannins and pathogen resistance

Colorectal cancer pathogenesis and progression isassociated with the presence of Fusobacteriumnucleatum and the reduction of acetylated deriva-tives of spermidine, as well as dietary componentssuch as tannin-rich foods. We show that a new tan-nase orthologue of F. nucleatum (TanBFnn) has sig-nicant structural differences with its Lactobacillusplantarum counterpart affecting the ap covering theactive site and the accessibility of substrates. Crys-tallographic and molecular dynamics analysisrevealed binding of polyamines to a small cavity thatconnects the active site with the bulk solvent whichinteract with catalytically indispensable residues. Asa result, spermidine and its derivatives, particularlyN8-acetylated spermidine, inhibit the hydrolytic activ-ity of TanBFnnand increase the toxicity of gallotan-nins to F. nucleatum. Our results support a model inwhich the balance between the detoxicant activity ofTanBFnnand the presence of metabolic inhibitorscan dictate either conducive or unfavourable condi-tions for the survival of F. nucleatum.

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Bibliographic Details
Main Authors: Mancheño, Jose M., Atondo, Estíbaliz, Tomás-Cortázar, Julen, Lavín, José Luis, Plaza-Vinuesa, Laura, Martín-Ruiz, Itziar, Barriales, Diego, Palacios, Ainhoa, Navo, Claudio D., Sampedro, Leticia, Peña-Cearra, Ainize, Pascual-Itoiz, Miguel Ángel, Castelo, Janire, Carreras-González, Ana, Castellana, Donatello, Pellón, Aize, Delgado, Susana, Ruas-Madiedo, Patricia, Rivas, Blanca de las, Abecia, Leticia, Muñoz, Rosario, Jiménez-Osés, Gonzalo, Anguita, Juan, Rodríguez, Héctor
Other Authors: Ministerio de Economía y Competitividad (España)
Format: artículo biblioteca
Language:English
Published: John Wiley & Sons 2022-01-18
Online Access:http://hdl.handle.net/10261/234876
http://dx.doi.org/10.13039/501100003086
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100011033
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Summary:Colorectal cancer pathogenesis and progression isassociated with the presence of Fusobacteriumnucleatum and the reduction of acetylated deriva-tives of spermidine, as well as dietary componentssuch as tannin-rich foods. We show that a new tan-nase orthologue of F. nucleatum (TanBFnn) has sig-nicant structural differences with its Lactobacillusplantarum counterpart affecting the ap covering theactive site and the accessibility of substrates. Crys-tallographic and molecular dynamics analysisrevealed binding of polyamines to a small cavity thatconnects the active site with the bulk solvent whichinteract with catalytically indispensable residues. Asa result, spermidine and its derivatives, particularlyN8-acetylated spermidine, inhibit the hydrolytic activ-ity of TanBFnnand increase the toxicity of gallotan-nins to F. nucleatum. Our results support a model inwhich the balance between the detoxicant activity ofTanBFnnand the presence of metabolic inhibitorscan dictate either conducive or unfavourable condi-tions for the survival of F. nucleatum.

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