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Structural investigation of syringomycin-E using molecular dynamics simulation and NMR

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Abstract

Syringomycin-E (SR-E) is a cyclic lipodepsinonapeptide produced by certain strains of the bacterium Pseudomonas syringae pv. syringae. It shows inhibitory effects against many fungal species, including human pathogens. Its primary biological target is the plasma membrane, where it forms channels comprised of at least six SR-E molecules. The high-resolution structure of SR-E and the structure of the channels are currently not known. In this paper, we investigate in atomic detail the molecular features of SR-E in water by NMR and in water and octane by molecular dynamics simulation (MD). We built a model of the peptide and examined its structure in water and octane in 200 ns MD simulations both with and without distance restraints derived from NMR NOE data. The resulting trajectories show good agreement with the measured NOEs and circular dichroism data from the literature and provide atomistic models of SR-E that are an important step toward a better understanding of the antifungal and antibacterial activity of this peptide.

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Acknowledgements

This work was supported by Hungarian Scientific Research Fund Grants F 043192, D 048670 and T 048713, by the Natural Science and Engineering Research Council of Canada and by AHFMR postdoctoral fellowships (Luca Monticelli, Zhitao Xu). DPT is an AHFMR Senior Scholar, CIHR New Investigator and Sloan Foundation Fellow. The authors are grateful to Professor Takemoto for providing SR-E for NMR measurements.

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Authors and Affiliations

  1. Institute of Biophysics and Radiation Biology, Semmelweis University, P.O. Box 263, 1444, Budapest, Hungary

    E. Mátyus, K. Blaskó & J. Fidy

  2. Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen, Hungary

    K. E. Kövér

  3. Department of Biological Sciences, University of Calgary, Calgary, Canada

    L. Monticelli, Z. Xu & D. P. Tieleman

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  1. E. Mátyus
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  2. L. Monticelli
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  3. K. E. Kövér
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  4. Z. Xu
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  5. K. Blaskó
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  6. J. Fidy
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  7. D. P. Tieleman
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Correspondence to E. Mátyus.

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Mátyus, E., Monticelli, L., Kövér, K.E. et al. Structural investigation of syringomycin-E using molecular dynamics simulation and NMR. Eur Biophys J 35, 459–467 (2006). https://doi.org/10.1007/s00249-006-0053-y

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  • DOI: https://doi.org/10.1007/s00249-006-0053-y

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