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Structure and mode of action of cyclic lipopeptide pseudofactin II with divalent metal ions

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Bibliographic Details
Summary:The interaction of natural lipopeptide pseudofactin II with a series of doubly charged metal cations was examined by matrixassisted laserdesorption ionizationtime of flight (MALDI-TOF) mass spectrometry and molecular modelling. The molecular modelling for metal-pseudofactin II provides information on the metalpeptide binding sites. Overall, Mg2+, Ca2+ and Zn2+ favor the association with oxygen atoms spanning the peptide backbone, whereas Cu2+ is coordinated by three nitrogens. Circular dichroism (CD) results confirmed that Zn2+ and Cu2+ can disrupt the secondary structure of pseudofactin II at high concentrations, while Ca2+ and Mg2+ did not essentially affect the structure of the lipopeptide. Interestingly, our results showed that the addition of Zn2+ and Cu2+ helped smaller micelles to form larger micellar aggregates. Since pseudofactin II binds metals, we tested whether this phenomena was somehow related to its antimicrobial activity against Staphylococcus epidermidis and Proteus mirabilis. We found that the antimicrobial effect of pseudofactin II was increased by supplementation of culture media with all tested divalent metal ions. Finally, by using Gram-positive and Gram-negative bacteria we showed that the higher antimicrobial activity of metal complexes of pseudofactin II is attributed to the disruption of the cytoplasmic membrane.
Main Authors:Janek, Tomasz
Other Authors:Rodrigues, L. R.; Gudiña, Eduardo J.; Czyznikowska, Zaneta
Subject:Lipopeptides Pseudofactin II Metal-ion interaction Circular dichroism Molecular modelling Uropathogenic microorganisms
Year:2016
Country:Portugal
Document type:article
Access type:open access
Associated institution:Universidade do Minho
Language:English
Origin:RepositóriUM - Universidade do Minho
Description
Summary:The interaction of natural lipopeptide pseudofactin II with a series of doubly charged metal cations was examined by matrixassisted laserdesorption ionizationtime of flight (MALDI-TOF) mass spectrometry and molecular modelling. The molecular modelling for metal-pseudofactin II provides information on the metalpeptide binding sites. Overall, Mg2+, Ca2+ and Zn2+ favor the association with oxygen atoms spanning the peptide backbone, whereas Cu2+ is coordinated by three nitrogens. Circular dichroism (CD) results confirmed that Zn2+ and Cu2+ can disrupt the secondary structure of pseudofactin II at high concentrations, while Ca2+ and Mg2+ did not essentially affect the structure of the lipopeptide. Interestingly, our results showed that the addition of Zn2+ and Cu2+ helped smaller micelles to form larger micellar aggregates. Since pseudofactin II binds metals, we tested whether this phenomena was somehow related to its antimicrobial activity against Staphylococcus epidermidis and Proteus mirabilis. We found that the antimicrobial effect of pseudofactin II was increased by supplementation of culture media with all tested divalent metal ions. Finally, by using Gram-positive and Gram-negative bacteria we showed that the higher antimicrobial activity of metal complexes of pseudofactin II is attributed to the disruption of the cytoplasmic membrane.