Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations

G. Trogen, Arto Annila, J. Eriksson, Maarit Kontteli, J. Meriluoto, I. Sethson, J. Zdunek, U. Edlund (Corresponding Author)

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Abstract

NMR spectroscopy in aqueous and dimethyl sulfoxide/water solutions is used to determine the three-dimensional structures of microcystin-LR, a cyclic cyanobacterial heptapeptide toxin which is a potent inhibitor of type 1 and type 2A protein phosphatases. The conformations of this toxic peptide are studied using a simulated annealing (SA) protocol followed by refined SA calculations in vacuo and free MD simulations in water. Only one conformational family in each solvent is found. The peptide ring has a saddle-shaped form, essentially the same in both solvents. The structural difference observed between the two solution structures is located to the part consisting of Mdha, Ala, and Leu. This peptide segment is not present in nodularin, a cyclic pentapeptide of similar toxicity. The Arg side chain is very flexible, while the side chain of Leu is well defined. The side chain of Adda, essential for toxicity, is constrained in the vicinity of the backbone ring but appears to be flexible in the more remote part.
Original languageEnglish
Pages (from-to)3197-3205
Number of pages9
JournalBiochemistry
Volume35
Issue number10
DOIs
Publication statusPublished - 1996
MoE publication typeA1 Journal article-refereed

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Molecular Dynamics Simulation
Nuclear magnetic resonance spectroscopy
Molecular dynamics
Magnetic Resonance Spectroscopy
Simulated annealing
Peptides
Toxicity
Protein Phosphatase 2
Water
Poisons
Dimethyl Sulfoxide
Conformations
cyanoginosin LR

Cite this

Trogen, G., Annila, A., Eriksson, J., Kontteli, M., Meriluoto, J., Sethson, I., ... Edlund, U. (1996). Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations. Biochemistry, 35(10), 3197-3205. https://doi.org/10.1021/bi952368s
Trogen, G. ; Annila, Arto ; Eriksson, J. ; Kontteli, Maarit ; Meriluoto, J. ; Sethson, I. ; Zdunek, J. ; Edlund, U. / Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations. In: Biochemistry. 1996 ; Vol. 35, No. 10. pp. 3197-3205.
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abstract = "NMR spectroscopy in aqueous and dimethyl sulfoxide/water solutions is used to determine the three-dimensional structures of microcystin-LR, a cyclic cyanobacterial heptapeptide toxin which is a potent inhibitor of type 1 and type 2A protein phosphatases. The conformations of this toxic peptide are studied using a simulated annealing (SA) protocol followed by refined SA calculations in vacuo and free MD simulations in water. Only one conformational family in each solvent is found. The peptide ring has a saddle-shaped form, essentially the same in both solvents. The structural difference observed between the two solution structures is located to the part consisting of Mdha, Ala, and Leu. This peptide segment is not present in nodularin, a cyclic pentapeptide of similar toxicity. The Arg side chain is very flexible, while the side chain of Leu is well defined. The side chain of Adda, essential for toxicity, is constrained in the vicinity of the backbone ring but appears to be flexible in the more remote part.",
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Trogen, G, Annila, A, Eriksson, J, Kontteli, M, Meriluoto, J, Sethson, I, Zdunek, J & Edlund, U 1996, 'Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations', Biochemistry, vol. 35, no. 10, pp. 3197-3205. https://doi.org/10.1021/bi952368s

Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations. / Trogen, G.; Annila, Arto; Eriksson, J.; Kontteli, Maarit; Meriluoto, J.; Sethson, I.; Zdunek, J.; Edlund, U. (Corresponding Author).

In: Biochemistry, Vol. 35, No. 10, 1996, p. 3197-3205.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations

AU - Trogen, G.

AU - Annila, Arto

AU - Eriksson, J.

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AU - Meriluoto, J.

AU - Sethson, I.

AU - Zdunek, J.

AU - Edlund, U.

PY - 1996

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N2 - NMR spectroscopy in aqueous and dimethyl sulfoxide/water solutions is used to determine the three-dimensional structures of microcystin-LR, a cyclic cyanobacterial heptapeptide toxin which is a potent inhibitor of type 1 and type 2A protein phosphatases. The conformations of this toxic peptide are studied using a simulated annealing (SA) protocol followed by refined SA calculations in vacuo and free MD simulations in water. Only one conformational family in each solvent is found. The peptide ring has a saddle-shaped form, essentially the same in both solvents. The structural difference observed between the two solution structures is located to the part consisting of Mdha, Ala, and Leu. This peptide segment is not present in nodularin, a cyclic pentapeptide of similar toxicity. The Arg side chain is very flexible, while the side chain of Leu is well defined. The side chain of Adda, essential for toxicity, is constrained in the vicinity of the backbone ring but appears to be flexible in the more remote part.

AB - NMR spectroscopy in aqueous and dimethyl sulfoxide/water solutions is used to determine the three-dimensional structures of microcystin-LR, a cyclic cyanobacterial heptapeptide toxin which is a potent inhibitor of type 1 and type 2A protein phosphatases. The conformations of this toxic peptide are studied using a simulated annealing (SA) protocol followed by refined SA calculations in vacuo and free MD simulations in water. Only one conformational family in each solvent is found. The peptide ring has a saddle-shaped form, essentially the same in both solvents. The structural difference observed between the two solution structures is located to the part consisting of Mdha, Ala, and Leu. This peptide segment is not present in nodularin, a cyclic pentapeptide of similar toxicity. The Arg side chain is very flexible, while the side chain of Leu is well defined. The side chain of Adda, essential for toxicity, is constrained in the vicinity of the backbone ring but appears to be flexible in the more remote part.

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Trogen G, Annila A, Eriksson J, Kontteli M, Meriluoto J, Sethson I et al. Conformational studies of microcystin-LR using NMR spectroscopy and molecular dynamics calculations. Biochemistry. 1996;35(10):3197-3205. https://doi.org/10.1021/bi952368s